thescientist--2020-11-02--The Past, Present, and Future of Lab Balances

Lab balances might sit more in the background for biologists , especially relative to chemists and physicists , but their importance should not be underestimated .
Aside from being absolutely integral to pharmacological studies and pharmaceutical development , accurate balance performance is essential to the consistent production of the routine buffers , medias , and other solutions that keep life science labs running smoothly day after day .
Dirk Ahlbrecht is the Head of Product Management Lab Weighing at Sartorius Lab Products and Services .
Currently based in Göttingen , Germany , Ahlbrecht has over 30 years of experience in @ @ @ @ @ @ @ various positions in service , sales , marketing , and product management during his tenure with Sartorius .
Ahlbrecht and his team of product managers oversees the development and life-cycle-management of Sartorius ’ global lab weighing portfolio .
What are your current priorities for improving balance technology ?
“ For a period roughly spanning the 1970s to the 1990s , we focused on expanding the technical capabilities of the instruments , ” said Ahlbrecht .
“ But now , we have reached a plateau .
Balances can provide measurements that are accurate to @ @ @ @ @ @ @ proven to be sufficient for most researcher needs .
Nowadays , topics other than technical specifications have grown in importance , such as integrating balances into weighing workflows and processes .
Balances today need to align with user needs .
“ We want to make sure that an instrument fits into the standard operating procedure ( SOP ) of a user ; the balance should behave in accordance with the user ’ s planning , ” Ahlbrecht stressed .
“ In many situations , researchers have to work within the constraints and limitations @ @ @ @ @ @ @ to flip the script and create something that could be modified and customized in order to integrate into a user ’ s SOP .
We ’ re not limiting this to the manual workflow—what a scientist does with their hands .
We also want to integrate our instruments into the full SOP , including the data workflow and any QA/QC elements.
” How do modern balances make life easier for scientists ?
Scientists in different fields have different needs when it comes to balance technology .
At the same time , there are @ @ @ @ @ @ @ .
Ahlbrecht brought up gravimetric dosing as an example : “ Gravimetric dosing , especially in smaller research labs , entails measuring many different samples once or a few times each .
This is much trickier than measuring one thing many times and it can result in errors.
” Ahlbrecht wants his instruments to help streamline this process .
“ For example , we can have the doors open and close automatically or we can create more ergonomically amenable weighing pans to make it easier to place powder into differently shaped vessels.
” @ @ @ @ @ @ @ it comes to weighing accuracy .
“ An error is probably 80 % environment and 20 % instrument , so we created assistance systems that help scientists avoid environment-related mistakes , ” said Ahlbrecht .
“ We offer education to inform users how measurements are affected by things like temperature , barometric pressure , and humidity .
But we also went beyond and placed sensors in the instrument to not only measure environmental conditions , but automatically re-adjust the balance according to the readings .
We want to make it so that scientists @ @ @ @ @ @ @ taking the powder out on a scoop and then putting it into the container.
” Amidst all these sensors and readings , it is crucial that balances remain accessible and easy to use .
Ahlbrecht emphasized that one of his main missions was to simplify the process .
“ I hate reading manuals .
Whenever I buy something and I have to read the manual , I return it , ” Ahlbrecht began .
“ We know that our instruments can do a lot and there are a lot of different configurations , @ @ @ @ @ @ @ interface in a self-explanatory way .
We want to make it similar to a cell phone or satellite navigation system where the buttons and icons are intuitive .
We ’ re currently working with an app concept where different applications guide various functionalities , and we ’ ve received a lot of positive feedback from users regarding its simplicity .
We also have a status center within our instruments that serves as a centralized troubleshooting and diagnostic dashboard so that our users can easily identify any technical or just obtain information about the @ @ @ @ @ @ @ is balance development advancing hand-in-hand with the scientific community ?
It is more imperative than ever to make sure design goals align with user needs .
“ The last millennium was shaped by pushing technical limits , but today it is a different race , ” Ahlbrecht said .
One area of emphasis is customizability .
“ Because the emphasis is now in the software as opposed to the engineering , our users can configure their instruments based on the functionality they need .
For example , for those in quality control , @ @ @ @ @ @ @ with regulatory compliance : password management , data encryption and transmission , that sort of thing .
But your average academic researcher won ’ t need this , so they can opt-out and not spend money on features they won ’ t use.
” Above all , Ahlbrecht stressed the importance of constant communication with scientists .
“ This is what we call ‘ voice of customer.
’ We have a system in place to regularly collect information and feedback even before we start development on something .
We go and talk to @ @ @ @ @ @ @ whether we are on the same wavelength , whether we are on the same page .
We collect this information through various channels , including sales , service , and marketing .
We even do joint product development with some of our clients if we identify a very specific need that has to be met .
Ultimately , we want to take many responsibilities and challenges off the shoulders of scientists so that they can focus on what ’ s most important to them.
” This article is brought to you by Sartorius @ @ @ @ @ @ @ international partner of biopharmaceutical research and the industry .
https : //www.sartorius.com/

Lab balances might sit more in the background for biologists, especially relative to chemists and physicists, but their importance should not be underestimated. Aside from being absolutely integral to pharmacological studies and pharmaceutical development, accurate balance performance is essential to the consistent development and production of excipients, buffers, medias, and other solutions that keep life science labs running smoothly day after day.
Dirk Ahlbrecht is the Head of Product Management Lab Weighing at Sartorius Lab Products and Services. Currently based in Göttingen, Germany, Ahlbrecht has over 30 years of experience in the lab balance business and has held various positions in service, sales, marketing, and product management during his tenure with Sartorius. Ahlbrecht and his team of product managers oversees the development and life-cycle-management of Sartorius’ global lab weighing portfolio.
What are your current priorities for improving balance technology?
“For a period roughly spanning the 1970s to the 1990s, we focused on expanding the technical capabilities of the instruments,” said Ahlbrecht. “But now, we have reached a plateau. Balances can provide measurements that are accurate to seven decimal points, and this has proven to be sufficient for most researcher needs. Nowadays, topics other than technical specifications have grown in importance, such as integrating balances into analytical workflows and processes.
Balances today need to align with user needs. “We want to make sure that an instrument fits into the standard operating procedure (SOP) of a user; the balance should behave in accordance with the user’s planning,” Ahlbrecht stressed. “In many situations, researchers have to work within the constraints and limitations of the instrument, and we wanted to flip the script and create something that could be modified and customized in order to integrate into a user’s SOP. We’re not limiting this to the manual workflow—what a scientist does with their hands. We also want to integrate our instruments into the full SOP, including the data workflow and any QA/QC elements.”
How do modern balances make life easier for scientists?
Scientists in different fields have different needs when it comes to balance technology. At the same time, there are a few applications that are relatively ubiquitous. Ahlbrecht brought up gravimetric dosing as an example: “Gravimetric dosing, especially in smaller research labs, entails measuring many different samples once or a few times each. This is much trickier than measuring one thing many times and it can result in errors.” Ahlbrecht wants his instruments to help streamline this process. “For example, we can have the doors open and close automatically or we can create more ergonomically amenable weighing pans to make it easier to place powder into differently shaped vessels.”
Environmental factors are a major concern when it comes to weighing accuracy. “An error is probably 80% environment and 20% instrument, so we created assistance systems that help scientists avoid environment-related mistakes,” said Ahlbrecht. “We offer education to inform users how measurements are affected by things like temperature, barometric pressure, and humidity. But we also went beyond and placed sensors in the instrument to not only measure environmental conditions, but automatically re-adjust the balance according to the readings. We want to make it so that scientists can focus on the important thing: taking the powder out on a scoop and then putting it into the container.”
Amidst all these sensors and readings, it is crucial that balances remain accessible and easy to use. Ahlbrecht emphasized that one of his main missions was to simplify the process. “I hate reading manuals. Whenever I buy something and I have to read the manual, I return it,” Ahlbrecht began. “We know that our instruments can do a lot and there are a lot of different configurations, so we have to design the user interface in a self-explanatory way. We want to make it similar to a cell phone or satellite navigation system where the buttons and icons are intuitive. We’re currently working with an app concept where different applications guide various functionalities, and we’ve received a lot of positive feedback from users regarding its simplicity. We also have a status center within our instruments that serves as a centralized troubleshooting and diagnostic dashboard so that our users can easily identify any technical or just obtain information about the current status of their balance.”
How is balance development advancing hand-in-hand with the scientific community?
It is more imperative than ever to make sure design goals align with user needs. “The last millennium was shaped by pushing technical limits, but today it is a different race,” Ahlbrecht said. One area of emphasis is customizability. “Because the emphasis is now in the software as opposed to the engineering, our users can configure their instruments based on the functionality they need. For example, for those in quality control, they can opt-in for software that helps with regulatory compliance: password management, data encryption and transmission, that sort of thing. But your average academic researcher won’t need this, so they can opt-out and not spend money on features they won’t use.”
Above all, Ahlbrecht stressed the importance of constant communication with scientists. “This is what we call ‘voice of customer.’ We have a system in place to regularly collect information and feedback even before we start development on something. We go and talk to users or do surveys to find out whether we are on the same wavelength, whether we are on the same page. We collect this information through various channels, including sales, service, and marketing. We even do joint product development with some of our clients if we identify a very specific need that has to be met. Ultimately, we want to take many responsibilities and challenges off the shoulders of scientists so that they can focus on what’s most important to them.”
Meet the Sponsor:
This article is brought to you by Sartorius. The Sartorius Group is a leading international partner of biopharmaceutical research and the industry. https://www.sartorius.com/


thescientist--2020-11-04--Paper Proposing COVID-19, Magnetism Link to Be Retracted

Update ( November 5 ) : The study is now marked as temporarily removed from Elsevier ’ s site .
A peer-reviewed paper suggesting that COVID-19 is caused not by SARS-CoV-2 but by magnetic anomalies will be retracted , the study ’ s first author and an editor from the journal that published it tell The Scientist .
The study , “ Can Traditional Chinese Medicine provide insights into controlling the COVID-19 pandemic : Serpentinization-induced lithospheric long-wavelength magnetic anomalies in Proterozoic bedrocks in a weakened geomagnetic field mediate the aberrant transformation of biogenic molecules in COVID-19 via magnetic catalysis , @ @ @ @ @ @ @ the Elsevier publication Science of the Total Environment on October 8 , but attracted widespread criticism beginning on October 29 , leading the University of Pittsburgh–based authors to request the retraction .
“ A paper like this gets out there , it ’ s published in some supposedly peer-reviewed journal—it makes the rest of the field look stupid , ” says Joe Kirschvink , a Caltech geobiologist whose research areas include sensing of magnetic fields by humans and other animals .
“ And that ’ s a harmful thing.
” The study ’ @ @ @ @ @ @ @ an assistant professor at the University of Pittsburgh Graduate School of Public Health who studies infectious disease , tells The Scientist that the origin for the research came late last year , when a few rats in his lab unexpectedly became very ill and had to be sacrificed .
“ I ’ ve been working with animals since my undergraduate days , ” he says , and hadn ’ t before seen an instance where “ in the matter of 12 hours , a healthy animal , just drops , can ’ t @ @ @ @ @ @ @ in search of an explanation , Bility saw changes to their lungs and kidneys that he thought were similar to injuries he ’ d read about in humans that were ascribed to vaping .
Bility began to suspect that there was a connection between the human vaping injuries and the pathology in the rats , which he suggests both stemmed from iron oxides in the lungs .
“ My argument was that the iron oxide that ’ s been deposited in these individuals ’ lungs [ from vaping ] is somehow interacting with @ @ @ @ @ @ @ says .
“ And that ’ s triggering this process called magnetic catalysis , basically , it has to do with spin chemistry .
And in our animals , somehow there ’ s some dysregulation—because they ’ re immunodeficient animals—in their iron that allows that same interaction to occur.
” Bility posted a preprint to ResearchGate in November of last year laying out the idea .
Asked why , if it was linked to immunodeficiency , the same phenomenon was not reported in immunodeficient humans , he says , “ I don ’ @ @ @ @ @ @ @ adding , “ I don ’ t know how well people have been looking.
” The group then had more rats die with the same pathology in February and March of this year , Bility says , and he connected the timing—close to the spring equinox , which he says is associated with changes in the geomagnetic field—to that of rising COVID-19 case numbers in the US .
In the paper , he and his coauthors propose that SARS-CoV-2 is a preexisting , endogenous virus in the human genome that is reawakened by @ @ @ @ @ @ @ ’ s magnetic field , but that the virus doesn ’ t cause the pathology seen in COVID-19 .
Rather , they suggest , the disease comes about due to other chemical reactions in the body catalyzed by the magnetic field .
Asked whether the SARS-CoV-2 sequence has been found in the human genome , Bility says , “ I ’ m not a genomic expert .
That was just something I did want to look at , but I did not look at that.
” Kirschvink says the paper contains multiple basic @ @ @ @ @ @ @ strong magnetic fields can indeed influence chemical reactions , the long-wavelength anomalies that are central to the study ’ s thesis are “ three or four orders of magnitude off ” from what would be required for such effects , he says .
“ This results section is a salad of different ideas taken out of context.
” The study also suggests , without experimental evidence , that jade amulets might protect wearers by countering the effects of the long-wavelength anomalies , an idea Bility says he based on records of practices by @ @ @ @ @ @ @ a period when geomagnetic conditions were similar to what they are now .
Kirschvink says the study ’ s description of jade ’ s magnetic properties is incorrect , and that in jade , “ the paramagnetic minerals are so weakly magnetized , they ’ re not going to do anything in these fields.
” Kirschvink says he ’ s heard from fellow geomagnetics researchers who “ are upset that their data is being used in a nonsensical way ” in the paper .
The study has also attracted derision on Twitter and @ @ @ @ @ @ @ Medicine extracellular vesicle researcher Kenneth Witwer was among those who criticized the paper on PubPeer , writing in part , “ Almost all symptoms were restricted to Room Number 1 of two adjacent rooms in Pittsburgh , suggesting that some agent such as an undetected pathogen was responsible for symptoms .
Effects of the earth ’ s magnetic field would presumably be similar in side-by-side rooms at the same facility.
” Witwer also wrote an email with the subject line “ virus denialism article : were you really involved ?
” on Friday @ @ @ @ @ @ @ , Yue Chen and Jean Nachega of the University of Pittsburgh Graduate School of Public Health .
In it , he calls the article “ pseudoscience ” and urges the authors to retract it immediately , adding that , “ I have also written to the department heads about this serious situation.
” Bility provided the email to The Scientist as an example of what he called an “ online mob ” that “ has been attempting to damage my career and that of my colleagues.
” For his part , Witwer writes @ @ @ @ @ @ @ “ The academy needs to be vigilant against pseudoscience and giving a voice to it.
” He ’ s concerned , he writes , that having such a paper published by scientists “ with real NIH funding and at a preeminent university ” might appear to validate specious claims that COVID-19 arises from some cause other than SARS-CoV-2 , which he compares to similar claims in the past about HIV/AIDS that “ led to public health disaster.
” Through a university spokesperson , Nachega declined to comment on the matter .
Bility says @ @ @ @ @ @ @ work has received , he regrets including his coauthors on the paper , and he takes full responsibility for its ideas .
His intention , he says , was not to undermine public health officials , but to propose a hypothesis for further discussion and investigation , and he plans to resubmit the paper as a sole author and without mentions of jade amulets or traditional Chinese medicine .
Both Witwer and Kirschvink say the paper ’ s publication represents a failure of peer review .
According to Damià Barceló , the editor @ @ @ @ @ @ @ handled the submission , it had two reviewers , a hydrogeologist and an epidemiologist-toxicologist .
In an email to The Scientist yesterday , he wrote that he expects the retraction will take hours or days to appear in Elsevier ’ s system , and that the resubmitted paper will need to be sent for peer review again before a final decision is made about its acceptance .

ABOVE: © ISTOCK.COM, ALXPIN
Update (November 5): The study is now marked as temporarily removed from Elsevier’s site.
A peer-reviewed paper suggesting that COVID-19 is caused not by SARS-CoV-2 but by magnetic anomalies will be retracted, the study’s first author and an editor from the journal that published it tell The Scientist. The study, “Can Traditional Chinese Medicine provide insights into controlling the COVID-19 pandemic: Serpentinization-induced lithospheric long-wavelength magnetic anomalies in Proterozoic bedrocks in a weakened geomagnetic field mediate the aberrant transformation of biogenic molecules in COVID-19 via magnetic catalysis,” was posted on the website of the Elsevier publication Science of the Total Environment on October 8, but attracted widespread criticism beginning on October 29, leading the University of Pittsburgh–based authors to request the retraction.
“A paper like this gets out there, it’s published in some supposedly peer-reviewed journal—it makes the rest of the field look stupid,” says Joe Kirschvink, a Caltech geobiologist whose research areas include sensing of magnetic fields by humans and other animals. “And that’s a harmful thing.”
The study’s first author, Moses Bility, an assistant professor at the University of Pittsburgh Graduate School of Public Health who studies infectious disease, tells The Scientist that the origin for the research came late last year, when a few rats in his lab unexpectedly became very ill and had to be sacrificed. “I’ve been working with animals since my undergraduate days,” he says, and hadn’t before seen an instance where “in the matter of 12 hours, a healthy animal, just drops, can’t breathe.” Examining the rats’ tissues in search of an explanation, Bility saw changes to their lungs and kidneys that he thought were similar to injuries he’d read about in humans that were ascribed to vaping.
Bility began to suspect that there was a connection between the human vaping injuries and the pathology in the rats, which he suggests both stemmed from iron oxides in the lungs. “My argument was that the iron oxide that’s been deposited in these individuals’ lungs [from vaping] is somehow interacting with the lithospheric magnetic field,” he says. “And that’s triggering this process called magnetic catalysis, basically, it has to do with spin chemistry. And in our animals, somehow there’s some dysregulation—because they’re immunodeficient animals—in their iron that allows that same interaction to occur.”
Bility posted a preprint to ResearchGate in November of last year laying out the idea. Asked why, if it was linked to immunodeficiency, the same phenomenon was not reported in immunodeficient humans, he says, “I don’t know all the answers,” adding, “I don’t know how well people have been looking.”
The group then had more rats die with the same pathology in February and March of this year, Bility says, and he connected the timing—close to the spring equinox, which he says is associated with changes in the geomagnetic field—to that of rising COVID-19 case numbers in the US. In the paper, he and his coauthors propose that SARS-CoV-2 is a preexisting, endogenous virus in the human genome that is reawakened by the effects of changes in the Earth’s magnetic field, but that the virus doesn’t cause the pathology seen in COVID-19. Rather, they suggest, the disease comes about due to other chemical reactions in the body catalyzed by the magnetic field. Asked whether the SARS-CoV-2 sequence has been found in the human genome, Bility says, “I’m not a genomic expert. That was just something I did want to look at, but I did not look at that.”
Kirschvink says the paper contains multiple basic errors. For example, while very strong magnetic fields can indeed influence chemical reactions, the long-wavelength anomalies that are central to the study’s thesis are “three or four orders of magnitude off” from what would be required for such effects, he says. “This results section is a salad of different ideas taken out of context.”
The study also suggests, without experimental evidence, that jade amulets might protect wearers by countering the effects of the long-wavelength anomalies, an idea Bility says he based on records of practices by ancient people in China and elsewhere during a period when geomagnetic conditions were similar to what they are now. Kirschvink says the study’s description of jade’s magnetic properties is incorrect, and that in jade, “the paramagnetic minerals are so weakly magnetized, they’re not going to do anything in these fields.”
Kirschvink says he’s heard from fellow geomagnetics researchers who “are upset that their data is being used in a nonsensical way” in the paper.
The study has also attracted derision on Twitter and PubPeer. Johns Hopkins University School of Medicine extracellular vesicle researcher Kenneth Witwer was among those who criticized the paper on PubPeer, writing in part, “Almost all symptoms were restricted to Room Number 1 of two adjacent rooms in Pittsburgh, suggesting that some agent such as an undetected pathogen was responsible for symptoms. Effects of the earth’s magnetic field would presumably be similar in side-by-side rooms at the same facility.”
Witwer also wrote an email with the subject line “virus denialism article: were you really involved?” on Friday to the paper’s senior authors, Yue Chen and Jean Nachega of the University of Pittsburgh Graduate School of Public Health. In it, he calls the article “pseudoscience” and urges the authors to retract it immediately, adding that, “I have also written to the department heads about this serious situation.” Bility provided the email to The Scientist as an example of what he called an “online mob” that “has been attempting to damage my career and that of my colleagues.”
For his part, Witwer writes in an email to The Scientist, “The academy needs to be vigilant against pseudoscience and giving a voice to it.” He’s concerned, he writes, that having such a paper published by scientists “with real NIH funding and at a preeminent university” might appear to validate specious claims that COVID-19 arises from some cause other than SARS-CoV-2, which he compares to similar claims in the past about HIV/AIDS that “led to public health disaster.”
Through a university spokesperson, Nachega declined to comment on the matter. Bility says that in light of the blowback his work has received, he regrets including his coauthors on the paper, and he takes full responsibility for its ideas. His intention, he says, was not to undermine public health officials, but to propose a hypothesis for further discussion and investigation, and he plans to resubmit the paper as a sole author and without mentions of jade amulets or traditional Chinese medicine.
Both Witwer and Kirschvink say the paper’s publication represents a failure of peer review. According to Damià Barceló, the editor at Science of the Total Environment who handled the submission, it had two reviewers, a hydrogeologist and an epidemiologist-toxicologist. In an email to The Scientist yesterday, he wrote that he expects the retraction will take hours or days to appear in Elsevier’s system, and that the resubmitted paper will need to be sent for peer review again before a final decision is made about its acceptance.


thescientist--2020-11-04--The Many Model Systems of COVID-19

The Many Model Systems of COVID-19

Earlier this year , as transmission of SARS-CoV-2 , the virus behind the COVID-19 pandemic , started to pick up speed , researchers around the world hurried to find model systems that could provide insight into disease spread , host immune responses , and possible treatments .
“ When the pandemic first started , nobody really knew what was going to be the best model , ” says Amanda Martinot , a veterinary pathologist at Tufts Cummings School of Veterinary Medicine .
The most widely available candidates were mice , which are easily housed and so well-researched that there are @ @ @ @ @ @ @ every aspect of their biology .
But as researchers suspected , based on previous incompatibility of mice and other coronaviruses , the animals present challenges when it comes to studying SARS-CoV-2 .
The virus uses a human receptor called ACE2 to get into cells , but mouse ACE2 is different enough that the virus doesn ’ t readily bind it .
Scientists have overcome the issue using two separate strategies : generating transgenic animals that express the human receptor and modifying the SARS-CoV-2 virus to make it better able to bind mouse ACE2 @ @ @ @ @ @ @ approaches , investigators have also been on the lookout for other options .
Ferrets , for instance , are useful for studying viral transmission and viral replication in the upper respiratory tract and have been used by several groups for SARS-CoV-2 experiments .
Some researchers have also turned to hamsters , which have been used in the past to study other viruses , including the coronaviruses responsible for severe acute respiratory syndrome and Middle East respiratory syndrome .
“ Hamsters are known in virology for their permissiveness to all kinds of viral infection @ @ @ @ @ @ @ of thumb , I would say if something doesn ’ t work in a mouse , you may as well try a hamster , ” says Jakob Trimpert , a postdoc at the Free University of Berlin .
“ And if you ’ re lucky , it works there.
” Along with collaborators , he ’ s been using several species of hamsters to study SARS-CoV-2 infections and potential therapeutics .
The hamster ACE2 receptor is compatible with SARS-CoV-2 , and the animals develop clear clinical indicators of disease , he explains .
@ @ @ @ @ @ @ auratus ) , one of the hamster species most commonly used in virus research worldwide , get mild SARS-CoV-2 infections , but their main symptom—weight loss—is reproducible and possible to measure .
These animals also have severe pneumonia that is detectable via lung pathology .
Trimpert and his colleagues used both transcriptomics and proteomics to evaluate the animals ’ immune responses to SARS-CoV-2 in a study they published on July 20 .
“ Hamsters have been the best model so far for showing us any clinical disease , ” says Martinot .
“ @ @ @ @ @ @ @ develop a fulminant pneumonia where it ’ s affecting sometimes over fifty percent of their lung , ” she adds .
“ They also will recover if given time , but the pathology we feel is more representative of what you might see in humans.
” Martinot , Dan Barouch , who directs the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center , and other collaborators recently published a study showing that a SARS-CoV-2 vaccine protected against weight loss and pneumonia in Syrian hamsters .
This species , also @ @ @ @ @ @ @ has some drawbacks , too , Trimpert says .
They ’ re big , for one , weighing in at 150–160 grams fully grown , in contrast to adult mice , which tip the scales at about 30–35 grams .
Syrian hamsters are also aggressive toward each other and sometimes the people taking care of them .
Their size and aggression mean that they often have to be housed alone in larger cages , which makes them more expensive to keep .
The biggest issues , according to Trimpert , are the poor @ @ @ @ @ @ @ just missing—and the lack of molecular tools that work in hamsters .
To circumvent these problems , Trimpert and his colleagues are resequencing and annotating the Syrian hamster genome .
Because the weight loss in Syrian hamsters—their only easily observable clinical symptom—is quite mild , it ’ s also a drawback , particularly when testing therapies or vaccines , Trimpert tells The Scientist .
“ If you need thirty hamsters in order to get statistical significance .
.
.
that is a huge practical problem.
” The researchers are skirting this issue by @ @ @ @ @ @ @ dwarf hamsters ( Phodopus roborovskii ) , which are smaller than mice and less aggressive than Syrian hamsters .
The dwarf hamsters also get much sicker than their larger relatives following SARS-CoV-2 infection , developing massive blood clots in the lungs , which are often present in severe cases of COVID-19 in people as well .
Most of these hamsters eventually die of the complications of the infection , which , according to Trimpert , indicates that they might be a good model of severe disease in humans .
Getting a better picture @ @ @ @ @ @ @ a common goal .
Eric Song , an MD/PhD student in Akiko Iwasaki ’ s lab at Yale School of Medicine , wanted to determine what effect SARS-CoV-2 was having on the brain .
He and his colleagues used a humanized mouse model , in which a promoter drives the expression of human ACE2 in epithelial cells , in a study released as a preprint earlier this year .
They found that SARS-CoV-2 could infect the central nervous system in the mice , but it still wasn ’ t clear whether those findings @ @ @ @ @ @ @ that question , the researchers turned to brain organoids—cultured , miniature organs that resemble the developing brain and contain neuronal and glial cell types derived from human induced pluripotent stem cells ( iPSCs ) .
Not only did SARS-CoV-2 infect the organoids , infection also appeared to cause cell death , a finding corroborated by another study in brain organoids published by separate group September 23 .
Song and his colleagues also found antibodies against SARS-CoV-2 in the cerebrospinal fluid of people with COVID-19 and evidence of SARS-CoV-2 infection in the post-mortem brains @ @ @ @ @ @ @ three complementary methods to account for the limitations of each , Song tells The Scientist .
“ There is room for all the different models that are in play , ” he adds .
With human samples , “ you can only take really a snapshot of the sickest patients because that ’ s the only time you will be getting a post-mortem sample , but combined with the mouse and the organoid model , you ’ re able to study [ the ] kinetics and the dynamic process of viral invasion .
@ @ @ @ @ @ @ tissues that we would not otherwise have access to.
” Immunologist and developmental biologist Hans Clevers of Utrecht University in the Netherlands and colleagues are leveraging that access with gut organoids .
Rather than deriving the organoids from iPSCs , though , they use multipotent stem cells taken from any adult epithelial tissue .
In some ways the strategy is more limited : gut epithelial cells can only make mini guts , for instance , in contrast to iPSC-derived organoids , which can become lots of different tissues .
On the other hand @ @ @ @ @ @ @ Clevers says .
“ iPSC-based organoids , you make them and then you have to use them for an experiment because they stop growing the moment you start specifying them.
” His group published a study on July 3 investigating whether or not SARS-CoV-2 can target the gut , a hypothesis based on the expression of ACE2 in the intestinal lining and the gastrointestinal symptoms that many COVID-19 patients experience .
Their work in human small intestinal organoids confirmed that the virus does enter the cells of the intestinal lining , replicate , @ @ @ @ @ @ @ Now , Clevers and his colleagues are using organoids to test possible COVID-19 therapeutics .
Chloroquine is an example of a drug that looked promising for blocking SARS-CoV-2 infection when researchers tried it in conventional cell culture—in that case , cells derived from African green monkey kidneys and grown in one layer on a dish , he says .
But , as they ’ ve shown in a new study that ’ s been submitted for peer review , in the gut organoid model chloroquine is ineffective against SARS-CoV-2 , just as it @ @ @ @ @ @ @ , this latest finding indicates that an extra screening step in organoids following the identification of a promising drug in a traditional cell culture system could provide another layer of information before moving into preclinical animal models or the clinic .
Cell lines are cheap , they grow fast , and most robotic strategies for screening have been designed for cells growing in two dimensions , Clevers says .
“ There are multiple efforts now around the world to come up with the machines to do similar high throughput screens with 3D .
@ @ @ @ @ @ @ a little bit more complex to analyze because they ’ re not flat , ” he explains , but the type of organoids they generate in his lab grow quickly .
He predicts that organoids will come to be used more widely because their physiology recapitulates that of humans so well , but that they ’ ll never replace animals .
Along with hamsters , nonhuman primates are one of the main models that researchers studying COVID-19 therapeutics use .
SARS-CoV-2 readily infects primates , such as macaques , due to the compatibility @ @ @ @ @ @ @ do not show disease symptoms , says Martinot .
The nonhuman primate experience of COVID-19 seems to be most similar to the mildly symptomatic cases of most people who are infected , she adds .
They develop regions of pathology in their lungs that are detectable with a microscope , but it ’ s not enough to make them sick , and observing that kind of disease in a person is unlikely because these animals are euthanized early in infection to allow researchers to track any changes .
“ It would be nice @ @ @ @ @ @ @ disease , ” says Barouch .
“ Nobody has been able to develop one so far , but models are always in development.
” And symptom presentation isn ’ t everything .
These animals are harder to access and harder to house than rodents , but “ they are a wonderful model for vaccine research and for evaluating .
.
.
the adaptive immune response to COVID-19 , ” Martinot says , at least in part because there are so many existing tools researchers can leverage .
“ Reagents that are available for @ @ @ @ @ @ @ ] work in monkeys , and so we can very carefully monitor the nonhuman primate for the development of antibodies , ” cytokine responses , and T-cell responses , she adds .
“ You always want to pick your best model for your specific question , ” Martinot tells The Scientist .
“ But depending on what kind of question you ’ re asking , or what kind of drug you ’ re testing , you really have to choose the model that best fits your ability to answer those questions in a @ @ @ @ @ @ @ World Health Organization ’ s Research & Development Blueprint Team has been working on this since February .
The team reviews progress and coordinates efforts on animal models of COVID-19 with the primary goal of advancing the development of COVID-19 therapeutics and vaccines .
On September 23 , some group members and a handful of other researchers published a review detailing the work that ’ s been done to model SARS-CoV-2 infections in animals—particularly , mice , hamsters , ferrets , and nonhuman primates—and highlighting how findings in animals correspond to disease progression @ @ @ @ @ @ @ use of these models is not a linear process , and they ’ re under constant revision , ” says Barouch , who is part of the WHO working group .
“ When there is human data , then that allows back validation or refinement of the model .
.
.
so there has to be a continuous feedback from models to clinical trials and back.
” “ In things that are so new , like SARS-CoV-2 , it may well be that there is more than one useful animal model , ” @ @ @ @ @ @ @ open and flexible , especially in emergency situations like this .
”

ABOVE: A golden Syrian hamster
© ISTOCK.COM, 4KODIAK
Earlier this year, as transmission of SARS-CoV-2, the virus behind the COVID-19 pandemic, started to pick up speed, researchers around the world hurried to find model systems that could provide insight into disease spread, host immune responses, and possible treatments.
“When the pandemic first started, nobody really knew what was going to be the best model,” says Amanda Martinot, a veterinary pathologist at Tufts Cummings School of Veterinary Medicine.
The most widely available candidates were mice, which are easily housed and so well-researched that there are tons of tools available for studying nearly every aspect of their biology. But as researchers suspected, based on previous incompatibility of mice and other coronaviruses, the animals present challenges when it comes to studying SARS-CoV-2. The virus uses a human receptor called ACE2 to get into cells, but mouse ACE2 is different enough that the virus doesn’t readily bind it.
Scientists have overcome the issue using two separate strategies: generating transgenic animals that express the human receptor and modifying the SARS-CoV-2 virus to make it better able to bind mouse ACE2.
Even with the success of those approaches, investigators have also been on the lookout for other options. Ferrets, for instance, are useful for studying viral transmission and viral replication in the upper respiratory tract and have been used by several groups for SARS-CoV-2 experiments. Some researchers have also turned to hamsters, which have been used in the past to study other viruses, including the coronaviruses responsible for severe acute respiratory syndrome and Middle East respiratory syndrome.
“Hamsters are known in virology for their permissiveness to all kinds of viral infection really, and, as a rule of thumb, I would say if something doesn’t work in a mouse, you may as well try a hamster,” says Jakob Trimpert, a postdoc at the Free University of Berlin. “And if you’re lucky, it works there.” Along with collaborators, he’s been using several species of hamsters to study SARS-CoV-2 infections and potential therapeutics.
The hamster ACE2 receptor is compatible with SARS-CoV-2, and the animals develop clear clinical indicators of disease, he explains. For instance, Syrian hamsters (Mesocricetus auratus), one of the hamster species most commonly used in virus research worldwide, get mild SARS-CoV-2 infections, but their main symptom—weight loss—is reproducible and possible to measure. These animals also have severe pneumonia that is detectable via lung pathology. Trimpert and his colleagues used both transcriptomics and proteomics to evaluate the animals’ immune responses to SARS-CoV-2 in a study they published on July 20.
Many alveolar air spaces (white) are collapsed during a SARS-CoV-2 lung infection in a Syrian hamster (right). They are not collapsed in an uninfected hamster’s lung (left). Amanda martinot, tufts cummings school of veterinary medicine
“Hamsters have been the best model so far for showing us any clinical disease,” says Martinot. “They develop weight loss, and they develop a fulminant pneumonia where it’s affecting sometimes over fifty percent of their lung,” she adds. “They also will recover if given time, but the pathology we feel is more representative of what you might see in humans.” Martinot, Dan Barouch, who directs the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center, and other collaborators recently published a study showing that a SARS-CoV-2 vaccine protected against weight loss and pneumonia in Syrian hamsters.
This species, also known as the golden Syrian hamster, has some drawbacks, too, Trimpert says. They’re big, for one, weighing in at 150–160 grams fully grown, in contrast to adult mice, which tip the scales at about 30–35 grams. Syrian hamsters are also aggressive toward each other and sometimes the people taking care of them. Their size and aggression mean that they often have to be housed alone in larger cages, which makes them more expensive to keep.
The biggest issues, according to Trimpert, are the poor quality of the sequenced genome—many genes are just missing—and the lack of molecular tools that work in hamsters. To circumvent these problems, Trimpert and his colleagues are resequencing and annotating the Syrian hamster genome.
Because the weight loss in Syrian hamsters—their only easily observable clinical symptom—is quite mild, it’s also a drawback, particularly when testing therapies or vaccines, Trimpert tells The Scientist. “If you need thirty hamsters in order to get statistical significance . . . that is a huge practical problem.”
The researchers are skirting this issue by beginning work with another species, Roborovski dwarf hamsters (Phodopus roborovskii), which are smaller than mice and less aggressive than Syrian hamsters. The dwarf hamsters also get much sicker than their larger relatives following SARS-CoV-2 infection, developing massive blood clots in the lungs, which are often present in severe cases of COVID-19 in people as well. Most of these hamsters eventually die of the complications of the infection, which, according to Trimpert, indicates that they might be a good model of severe disease in humans.
Organoids in addition to animal models
A human intestinal organoid (with nuclei labeled in blue and cell shape outlined in green) infected with SARS-CoV-2 (labeled in red) Joep Beumer
Getting a better picture of what is happening in people is a common goal. Eric Song, an MD/PhD student in Akiko Iwasaki’s lab at Yale School of Medicine, wanted to determine what effect SARS-CoV-2 was having on the brain. He and his colleagues used a humanized mouse model, in which a promoter drives the expression of human ACE2 in epithelial cells, in a study released as a preprint earlier this year. They found that SARS-CoV-2 could infect the central nervous system in the mice, but it still wasn’t clear whether those findings translated to human patients.
To probe that question, the researchers turned to brain organoids—cultured, miniature organs that resemble the developing brain and contain neuronal and glial cell types derived from human induced pluripotent stem cells (iPSCs). Not only did SARS-CoV-2 infect the organoids, infection also appeared to cause cell death, a finding corroborated by another study in brain organoids published by separate group September 23. Song and his colleagues also found antibodies against SARS-CoV-2 in the cerebrospinal fluid of people with COVID-19 and evidence of SARS-CoV-2 infection in the post-mortem brains of COVID-19 patients.
The team used three complementary methods to account for the limitations of each, Song tells The Scientist. “There is room for all the different models that are in play,” he adds. With human samples, “you can only take really a snapshot of the sickest patients because that’s the only time you will be getting a post-mortem sample, but combined with the mouse and the organoid model, you’re able to study [the] kinetics and the dynamic process of viral invasion. Things like organoids really help us access tissues that we would not otherwise have access to.”
Immunologist and developmental biologist Hans Clevers of Utrecht University in the Netherlands and colleagues are leveraging that access with gut organoids. Rather than deriving the organoids from iPSCs, though, they use multipotent stem cells taken from any adult epithelial tissue. In some ways the strategy is more limited: gut epithelial cells can only make mini guts, for instance, in contrast to iPSC-derived organoids, which can become lots of different tissues. On the other hand, “they grow forever,” Clevers says. “iPSC-based organoids, you make them and then you have to use them for an experiment because they stop growing the moment you start specifying them.”
His group published a study on July 3 investigating whether or not SARS-CoV-2 can target the gut, a hypothesis based on the expression of ACE2 in the intestinal lining and the gastrointestinal symptoms that many COVID-19 patients experience. Their work in human small intestinal organoids confirmed that the virus does enter the cells of the intestinal lining, replicate, and cause changes in gene expression.
Now, Clevers and his colleagues are using organoids to test possible COVID-19 therapeutics. Chloroquine is an example of a drug that looked promising for blocking SARS-CoV-2 infection when researchers tried it in conventional cell culture—in that case, cells derived from African green monkey kidneys and grown in one layer on a dish, he says. But, as they’ve shown in a new study that’s been submitted for peer review, in the gut organoid model chloroquine is ineffective against SARS-CoV-2, just as it is in patients. According to Clevers, this latest finding indicates that an extra screening step in organoids following the identification of a promising drug in a traditional cell culture system could provide another layer of information before moving into preclinical animal models or the clinic.
Cell lines are cheap, they grow fast, and most robotic strategies for screening have been designed for cells growing in two dimensions, Clevers says. “There are multiple efforts now around the world to come up with the machines to do similar high throughput screens with 3D. With the organoids, it’s a little bit more complex to analyze because they’re not flat,” he explains, but the type of organoids they generate in his lab grow quickly. He predicts that organoids will come to be used more widely because their physiology recapitulates that of humans so well, but that they’ll never replace animals.
SARS-CoV-2 in nonhuman primates
Along with hamsters, nonhuman primates are one of the main models that researchers studying COVID-19 therapeutics use. SARS-CoV-2 readily infects primates, such as macaques, due to the compatibility of their ACE2 receptor, but they do not show disease symptoms, says Martinot. The nonhuman primate experience of COVID-19 seems to be most similar to the mildly symptomatic cases of most people who are infected, she adds. They develop regions of pathology in their lungs that are detectable with a microscope, but it’s not enough to make them sick, and observing that kind of disease in a person is unlikely because these animals are euthanized early in infection to allow researchers to track any changes.
“It would be nice to have a primate model of severe disease,” says Barouch. “Nobody has been able to develop one so far, but models are always in development.”
And symptom presentation isn’t everything. These animals are harder to access and harder to house than rodents, but “they are a wonderful model for vaccine research and for evaluating . . . the adaptive immune response to COVID-19,” Martinot says, at least in part because there are so many existing tools researchers can leverage. “Reagents that are available for evaluating the immune response [in people] work in monkeys, and so we can very carefully monitor the nonhuman primate for the development of antibodies,” cytokine responses, and T-cell responses, she adds.
“You always want to pick your best model for your specific question,” Martinot tells The Scientist. “But depending on what kind of question you’re asking, or what kind of drug you’re testing, you really have to choose the model that best fits your ability to answer those questions in a very accurate and reproducible way.”
The World Health Organization’s Research & Development Blueprint Team has been working on this since February. The team reviews progress and coordinates efforts on animal models of COVID-19 with the primary goal of advancing the development of COVID-19 therapeutics and vaccines. On September 23, some group members and a handful of other researchers published a review detailing the work that’s been done to model SARS-CoV-2 infections in animals—particularly, mice, hamsters, ferrets, and nonhuman primates—and highlighting how findings in animals correspond to disease progression in people.
“The development and use of these models is not a linear process, and they’re under constant revision,” says Barouch, who is part of the WHO working group. “When there is human data, then that allows back validation or refinement of the model . . . so there has to be a continuous feedback from models to clinical trials and back.”
“In things that are so new, like SARS-CoV-2, it may well be that there is more than one useful animal model,” Trimpert says. “We should be open and flexible, especially in emergency situations like this.”


thescientist--2020-11-04--Mining Coding Regions with Whole-Exome Sequencing

The human genome contains roughly three billion base pairs , but only 1-5 % of these encode functional proteins .
@ @ @ @ @ ) provides rich information about single nucleotide , structural , or copy number variants across @ @ @ @ @ time- and resource-intensive .
Thus , scientists who study mutations in coding regions or in @ @ @ @ @ often rely on targeted NGS panels .
Options for targeted panels include exome panels for @ @ @ @ @ as well as more precise , custom-designed panels .
Download this ebook from The Scientist @ @ @ @ @ Roche to discover • The differences between WGS , WES , and custom panels • @ @ @ @ @ challenges with WES and custom panels

The human genome contains roughly three billion base pairs, but only 1-5% of these encode functional proteins. Although whole-genome sequencing (WGS) provides rich information about single nucleotide, structural, or copy number variants across the genome, it is time- and resource-intensive. Thus, scientists who study mutations in coding regions or in subsets of specific disease-associated genes often rely on targeted NGS panels. Options for targeted panels include exome panels for whole-exome sequencing (WES) as well as more precise, custom-designed panels.
Download this ebook from The Scientist's Creative Services team and Roche to discover


thescientist--2020-11-04--Cell Biologist Angelika Amon Dies at 53

Cell Biologist Angelika Amon Dies at 53

Angelika Amon , a cell biologist at MIT who was known for her research on the cellular effects of aneuploidy , an abnormal number of chromosomes , and their contribution to tumor formation , died October 29 from ovarian cancer .
She was 53 years old .
“ More than anyone else I ’ ve ever met , she was an absolute force of nature , ” says MIT biologist Matthew Vander Heiden , whose lab was adjacent to Amon ’ s and who considered her a close friend .
“ She just has this larger than life personality—there ’ @ @ @ @ @ @ @ ” Born in Vienna , Austria , in 1967 , Amon had always been interested in biology and animals , setting her sights on pursuing zoology .
But in high school , Amon saw an old black-and-white film about chromosome segregation and was taken aback by the sister chromatids splitting apart , according to an MIT obituary .
She took this curiosity to the University of Vienna , where she studied genetics .
She continued her studies there for graduate school under the mentorship of Kim Nasmyth .
For her PhD , Amon @ @ @ @ @ @ @ major discoveries about the cell cycle , says Cold Spring Harbor Laboratory biologist Jason Sheltzer , who worked as a doctoral student in Amon ’ s lab .
Chiefly , she uncovered that cyclins , which are proteins that accumulate within cells as they enter mitosis , must break down before cells progress from mitosis to G1 .
After earning her doctorate in 1993 , Amon worked at the University of Vienna for another year before moving to the US and turning her focus to fruit flies in her research as a postdoc @ @ @ @ @ @ @ MIT ’ s Whitehead Institute for Biomedical Research .
In 1996 , she was named a Whitehead Fellow , a program that offers recent doctorates mentorship to undertake their own investigations .
There , she discovered that the enzyme Cdc14 , found in the nucleolus of cells , prompts cells to exit mitosis .
“ I don ’ t think anyone really studied how cells exited mitosis before her , ” says Sheltzer .
Amon went on to a faculty position in 1999 at MIT ’ s Koch Institute for Integrative Cancer Research @ @ @ @ @ @ @ cause stress in protein folding and cell metabolism , which leads to errors in those processes and can drive cancer .
Much of Amon ’ s work also focused on chromosome segregation , one of the last steps of cell division , and what happens after an error in this process .
“ Everyone had assumed for 50 years that chromosome segregation errors are bad—if something goes wrong in mitosis , that ’ ll be bad for the cells , ” says Sheltzer .
“ She was the first person who thought , @ @ @ @ @ @ @ t know what happens after a chromosome segregation error.
’ ” Her lab also demonstrated that cells can become too big to reproduce and reenter the cell cycle , contributing to senescence and tissue aging .
In a preprint posted two days before her death , Amon and her colleagues show that hematopoietic stem cells ’ small size is key to their ability to function and reproduce .
“ She was just in her early 50s—she was really cut off at the prime of her research career , ” says Sheltzer .
While @ @ @ @ @ @ @ research , Vander Heiden says , her demeanor set her apart from other researchers .
“ Everyone knows science is filled with a lot of bullshit everywhere , and she would cut through the bullshit always and say things for what they are , and that was incredibly refreshing.
” Sheltzer recalls that when MIT ’ s president L. Rafael Reif faced pressure for accepting donations from convicted sex offender and financier Jeffrey Epstein , Amon stood up at a faculty meeting and called on Reif to resign .
“ That was evidence @ @ @ @ @ @ @ at all , ” says Sheltzer , noting that Amon was the only faculty member in cancer research to call for Reif ’ s resignation .
“ She called people out , even if they were her boss ’ s boss ’ s boss , for what she thought was unethical behavior.
” Sheltzer says working in Amon ’ s lab made him not only a better researcher , but also a better mentor by encouraging everyone to be well-rounded individuals .
“ MIT was full of smart people , but that didn @ @ @ @ @ @ @ says .
“ Angelika thought the real thing that separated people was how persistently they took on a problem and how hard they worked.
” For her research , Amon received the 2003 National Science Foundation Alan T. Waterman Award , the 2007 Paul Marks Prize for Cancer Research , the 2008 National Academy of Sciences Award in Molecular Biology , and the 2013 Ernst Jung Prize for Medicine .
In 2019 , she won the Breakthrough Prize in Life Sciences and the Vilcek Prize in Biomedical Science and this year , she @ @ @ @ @ @ @ Award .
Amon is survived by her husband Johannes Weis , her daughters Theresa and Clara Weis , and her three siblings and their families .

Angelika Amon Samara Vise, koch institute at mit
Angelika Amon, a cell biologist at MIT who was known for her research on the cellular effects of aneuploidy, an abnormal number of chromosomes, and their contribution to tumor formation, died October 29 from ovarian cancer. She was 53 years old.
“More than anyone else I’ve ever met, she was an absolute force of nature,” says MIT biologist Matthew Vander Heiden, whose lab was adjacent to Amon’s and who considered her a close friend. “She just has this larger than life personality—there’s no other way to put it.”
Born in Vienna, Austria, in 1967, Amon had always been interested in biology and animals, setting her sights on pursuing zoology. But in high school, Amon saw an old black-and-white film about chromosome segregation and was taken aback by the sister chromatids splitting apart, according to an MIT obituary. She took this curiosity to the University of Vienna, where she studied genetics. She continued her studies there for graduate school under the mentorship of Kim Nasmyth.
For her PhD, Amon studied cell division in yeast and made major discoveries about the cell cycle, says Cold Spring Harbor Laboratory biologist Jason Sheltzer, who worked as a doctoral student in Amon’s lab. Chiefly, she uncovered that cyclins, which are proteins that accumulate within cells as they enter mitosis, must break down before cells progress from mitosis to G1.
After earning her doctorate in 1993, Amon worked at the University of Vienna for another year before moving to the US and turning her focus to fruit flies in her research as a postdoc in Ruth Lehmann’s lab at MIT’s Whitehead Institute for Biomedical Research. In 1996, she was named a Whitehead Fellow, a program that offers recent doctorates mentorship to undertake their own investigations. There, she discovered that the enzyme Cdc14, found in the nucleolus of cells, prompts cells to exit mitosis.
“I don’t think anyone really studied how cells exited mitosis before her,” says Sheltzer.
Amon went on to a faculty position in 1999 at MIT’s Koch Institute for Integrative Cancer Research, where she found that extra chromosomes cause stress in protein folding and cell metabolism, which leads to errors in those processes and can drive cancer. Much of Amon’s work also focused on chromosome segregation, one of the last steps of cell division, and what happens after an error in this process.
“Everyone had assumed for 50 years that chromosome segregation errors are bad—if something goes wrong in mitosis, that’ll be bad for the cells,” says Sheltzer. “She was the first person who thought, ‘Well, we actually don’t know what happens after a chromosome segregation error.’”
Her lab also demonstrated that cells can become too big to reproduce and reenter the cell cycle, contributing to senescence and tissue aging. In a preprint posted two days before her death, Amon and her colleagues show that hematopoietic stem cells’ small size is key to their ability to function and reproduce.
“She was just in her early 50s—she was really cut off at the prime of her research career,” says Sheltzer.
While Amon was revered at MIT for her research, Vander Heiden says, her demeanor set her apart from other researchers. “Everyone knows science is filled with a lot of bullshit everywhere, and she would cut through the bullshit always and say things for what they are, and that was incredibly refreshing.”
Sheltzer recalls that when MIT’s president L. Rafael Reif faced pressure for accepting donations from convicted sex offender and financier Jeffrey Epstein, Amon stood up at a faculty meeting and called on Reif to resign. “That was evidence that she didn’t tolerate bullshit at all,” says Sheltzer, noting that Amon was the only faculty member in cancer research to call for Reif’s resignation. “She called people out, even if they were her boss’s boss’s boss, for what she thought was unethical behavior.”
Sheltzer says working in Amon’s lab made him not only a better researcher, but also a better mentor by encouraging everyone to be well-rounded individuals. “MIT was full of smart people, but that didn’t mean anything,” he says. “Angelika thought the real thing that separated people was how persistently they took on a problem and how hard they worked.”
For her research, Amon received the 2003 National Science Foundation Alan T. Waterman Award, the 2007 Paul Marks Prize for Cancer Research, the 2008 National Academy of Sciences Award in Molecular Biology, and the 2013 Ernst Jung Prize for Medicine. In 2019, she won the Breakthrough Prize in Life Sciences and the Vilcek Prize in Biomedical Science and this year, she received the Human Frontier Science Program Nakasone Award.
Amon is survived by her husband Johannes Weis, her daughters Theresa and Clara Weis, and her three siblings and their families.


thescientist--2020-11-03--The Specter of Endothelial Injury in COVID-19

In early March , in a conference call with researchers in China , hematologist Alfred Lee , George Goshua , and others at the Yale School of Medicine were forewarned about an unusual finding in COVID-19 patients in advanced stages of the disease .
Doctors were observing ischemic digits , or black fingers and toes .
To Lee and Goshua , this sounded like a microvascular thrombosis , minute blood clots in small blood vessels .
A few weeks later , the Yale physicians were confronted with their first COVID-19 death , ostensibly due to a major blood clot in @ @ @ @ @ @ @ prompted them to set up a panel of clotting tests for COVID-19 patients .
What came back was something Lee had never seen before : levels of the von Willebrand factor ( VWF ) , a protein involved in blood clotting , were through the roof ; they had surpassed the upper limit of detection of the laboratory assay the group was using .
Because VWF is released from endothelial cells that line blood vessels , Lee ’ s natural inference was that the endothelium was somehow damaged and releasing enormous amounts of @ @ @ @ @ @ @ clots .
The Yale team then ran a series of screens for other markers of endothelial damage on 68 COVID-19 patients , and the results published in The Lancet Haematology in June show that proteins such as soluble P-selectin were also elevated in critically ill COVID-19 patients compared with healthy controls .
One of the markers , soluble thrombomodulin , even correlated with how long patients stayed in the hospital and whether they died .
From these data , the investigators deduced that endothelial injury is linked to disease severity in COVID-19 and @ @ @ @ @ @ @ could improve disease outcomes .
It ’ s impossible to say which came first—the coronavirus infection or the endothelial damage , which is a known feature of diabetes , hypertension , and other diseases , notes Miriam Merad , an immunologist at the Icahn School of Medicine at Mount Sinai in New York who was not involved in the study .
Conditions such as diabetes , hypertension , obesity , and aging—comorbidities present among Lee ’ s COVID-19 patients—could have also played a part in the vascular damage , she adds .
Still @ @ @ @ @ @ @ is very important [ in COVID-19 ] , ” she tells The Scientist .
Goshua comments that to be able to see an endothelial cell signal despite having only one blood sample per patient was something quite profound .
In fact , researchers have come to view the vasculature as the tissue most vulnerable to damage from SARS-CoV-2 infection , Thomas Lüscher , a cardiologist at Imperial College London who has been studying the endothelium for more than three decades , tells The Scientist .
“ The concept that the endothelium is the @ @ @ @ @ @ @ very important.
” Endothelial cells in the lungs play a central role in orchestrating damage to this organ , which is the chief target of the SARS-CoV-2 .
The endothelium as a common theme in COVID-19 The endothelium comprises a single layer of cells that forms the interior lining of blood vessels throughout the body .
The tissue physically insulates blood elements from the highly thrombogenic , or clot-promoting , subendothelial connective tissue .
In addition , under normal conditions , blood cells flow past without getting stuck because of the balance between @ @ @ @ @ @ @ endothelium .
“ The endothelium is like Teflon .
Nothing sticks to it , ” Harvard Medical School ’ s Denisa Wagner tells The Scientist .
But just as a Teflon pan becomes sticky when scratched , a host of factors—including viral infection and encounters with agents of inflammation—makes it sticky .
Such insults trigger endothelial release of VWF , which tethers platelets—cells involved in clotting—to the vessel wall , while the elevation of P-selectin causes leukocytes or immune cells to stick to the endothelium as well .
This sets in motion a @ @ @ @ @ @ @ and inflammation—two defining features of severe SARS-CoV-2 infection .
See “ Autopsies Indicate Blood Clots Are Lethal in COVID-19 ” Pathology and autopsy studies have found particles of SARS-CoV-2 inside endothelial cells , and a growing body of evidence suggests that the endothelium plays a key role in the disease .
In the early days of the pandemic , doctors discovered that damage to the endothelial lining in the lungs was associated with the fluid leakage and acute respiratory distress syndrome .
Following this , researchers linked blood clots in the lungs and @ @ @ @ @ @ @ found viral particles in endothelial cells in organs other than the lungs , such as the kidneys .
Thus , damage to the endothelium and the ensuing clotting and inflammation emerged as potential drivers of the strokes , cardiac injury , kidney disease , and other features of the disease .
“ The protean manifestations of COVID-19 strongly implicate activation and dysfunction of the endothelium ” as a unifying consequence of infection , “ which can help us frame our thinking about the disease [ mechanism ] , ” says Peter Libby , @ @ @ @ @ @ @ who has been studying the endothelium for nearly 40 years .
He adds that this hypothesis “ helps [ us ] understand why this disease so perniciously affects so many different organ systems.
” This hypothesis has been primarily based on clinical observations .
Lee ’ s finding of high VWF levels and another study from Western University ’ s Douglas Fraser offer the best mechanistic evidence .
Fraser and his colleagues tracked endothelial markers in 10 ICU patients with COVID-19 , 10 ICU patients who were hospitalized for other reasons , and @ @ @ @ @ @ @ results similar to Lee ’ s investigation , such as raised plasma VWF and soluble P-selectin levels .
In addition , Fraser and his colleagues noted telltale signs of damage to the glycocalyx , a moss-like molecular coating that envelops the endothelium , in COVID-19 patients .
Aaron Petrey , an immunologist and glycobiologist at the University of Utah School of Medicine , says that glycocalyx degradation and shedding is a theme in sepsis—which can occur in COVID-19—so “ it ’ s unclear if this is a unique feature of COVID-19.
” Wagner @ @ @ @ @ @ @ close to 40 years , tells The Scientist that both studies are a very good beginning to studying the endothelium in COVID-19 .
She says the finding that VWF is majorly increased is particularly noteworthy .
“ That , I think , is super important ” to the increased tendency for clotting seen in COVID-19 patients .
Fraser , who published the results in August , says keeping close watch on endothelial cell markers and glycocalyx degradation could aid doctors in treating COVID-19 patients , alerting them to when it ’ s time @ @ @ @ @ @ @ .
Libby adds that these endothelial indicators also give doctors tools to assess which patients are likely to develop a blood clot and therefore should be treated with appropriate medications , such as blood thinners .
See “ Could Statins Reduce the Severity of COVID-19 ?
” A few other reports from France , Germany , and China that have looked at various markers of endothelial and glycocalyx damage , both in vitro and in vivo , link endothelial damage to the severity of disease .
All these studies bear witness to the @ @ @ @ @ @ @ , who was not involved in any of these studies , says these interrogations of the endothelium “ are stimulating , but they are not solving the problem yet .
What ’ s the first step that initiates this cascade of events ?
That ’ s the real question—that hasn ’ t been solved yet.
” A motley of studies are looking at ways to restore endothelial integrity in COVID-19 patients using various agents , including P-selectin blockers .
Targeting the complement cascade—an inflammatory pathway that causes endothelial dysfunction—is another approach in clinical @ @ @ @ @ @ @ trial recently attesting to the safety and tolerability of anti-complement therapy and reporting early efficacy signals .
Breaking up strings of VWF is yet another tactic that might work , says Wagner .
As endothelial cells release abundant amounts of VWF , the molecules can self-associate and clog small blood vessels , but an enzyme present in plasma called ADAMTS13 chops up clusters of VWF .
In COVID-19 , ADAMTS13 levels plummet and , along with extremely high VWF levels , portends severe disease .
It ’ s “ a recipe for trouble @ @ @ @ @ @ @ believe that supplying ADAMTS13 to COVID-19 patients with high VWF would significantly reduce thrombosis and organ damage.
” Currently , recombinant ADAMTS13 is being trialled in thrombotic thrombocytopenic purpura , a condition where ADAMTS13 deficiency leads to excess VWF and minute clots form in small blood vessels , but so far is not being tested in COVID-19 patients .
Christian Con Yost , a pediatrician at the University of Utah School of Medicine , tells The Scientist that breaking down these large VWF aggregates might also tame the downstream inflammation and accumulation of @ @ @ @ @ @ @ the VWF/ADAMTS13 axis is worth further investigation .
“ We ’ re looking at this very closely , ” he says .
Lüscher , Libby , and other endothelial experts assert that targeting the two primary pathways to which the endothelium is intricately linked—hyperinflammation and clotting—would be the most beneficial .
Reflecting on the current status of these two types of therapies , Libby says that the clinical research field is still in the era of non-randomized observational data and that outcomes of randomized placebo-controlled trials are desperately needed .
“ It ’ @ @ @ @ @ @ @ ’ m not sure that [ it ] will be sufficient to change the course of the disease , ” Lüscher says of these diverse approaches to address endothelial mayhem .
“ This is not a very specific infection .
There are many pathways .
That ’ s the dilemma.
” Jamie O ’ Sullivan , a vascular biologist at the Royal College of Surgeons in Ireland , explains to The Scientist in an email : “ Targeting these pathways in isolation may ameliorate disease severity but is unlikely to completely attenuate disease @ @ @

ABOVE: © ISTOCK.COM, DESIGN CELLS
In early March, in a conference call with researchers in China, hematologist Alfred Lee, George Goshua, and others at the Yale School of Medicine were forewarned about an unusual finding in COVID-19 patients in advanced stages of the disease. Doctors were observing ischemic digits, or black fingers and toes. To Lee and Goshua, this sounded like a microvascular thrombosis, minute blood clots in small blood vessels. A few weeks later, the Yale physicians were confronted with their first COVID-19 death, ostensibly due to a major blood clot in the patient’s lung, which prompted them to set up a panel of clotting tests for COVID-19 patients.
What came back was something Lee had never seen before: levels of the von Willebrand factor (VWF), a protein involved in blood clotting, were through the roof; they had surpassed the upper limit of detection of the laboratory assay the group was using. Because VWF is released from endothelial cells that line blood vessels, Lee’s natural inference was that the endothelium was somehow damaged and releasing enormous amounts of VWF that was then contributing to blood clots.
The Yale team then ran a series of screens for other markers of endothelial damage on 68 COVID-19 patients, and the results published in The Lancet Haematology in June show that proteins such as soluble P-selectin were also elevated in critically ill COVID-19 patients compared with healthy controls. One of the markers, soluble thrombomodulin, even correlated with how long patients stayed in the hospital and whether they died. From these data, the investigators deduced that endothelial injury is linked to disease severity in COVID-19 and that strategies geared toward palliating this damage could improve disease outcomes.
It’s impossible to say which came first—the coronavirus infection or the endothelial damage, which is a known feature of diabetes, hypertension, and other diseases, notes Miriam Merad, an immunologist at the Icahn School of Medicine at Mount Sinai in New York who was not involved in the study. Conditions such as diabetes, hypertension, obesity, and aging—comorbidities present among Lee’s COVID-19 patients—could have also played a part in the vascular damage, she adds. Still, “I think studying the vasculature is very important [in COVID-19],” she tells The Scientist.
Goshua comments that to be able to see an endothelial cell signal despite having only one blood sample per patient was something quite profound. In fact, researchers have come to view the vasculature as the tissue most vulnerable to damage from SARS-CoV-2 infection, Thomas Lüscher, a cardiologist at Imperial College London who has been studying the endothelium for more than three decades, tells The Scientist. “The concept that the endothelium is the main target of this virus is really very important.” Endothelial cells in the lungs play a central role in orchestrating damage to this organ, which is the chief target of the SARS-CoV-2.
The endothelium as a common theme in COVID-19
The endothelium comprises a single layer of cells that forms the interior lining of blood vessels throughout the body. The tissue physically insulates blood elements from the highly thrombogenic, or clot-promoting, subendothelial connective tissue. In addition, under normal conditions, blood cells flow past without getting stuck because of the balance between the pro- and anti-clotting properties of the endothelium.
“The endothelium is like Teflon. Nothing sticks to it,” Harvard Medical School’s Denisa Wagner tells The Scientist. But just as a Teflon pan becomes sticky when scratched, a host of factors—including viral infection and encounters with agents of inflammation—makes it sticky. Such insults trigger endothelial release of VWF, which tethers platelets—cells involved in clotting—to the vessel wall, while the elevation of P-selectin causes leukocytes or immune cells to stick to the endothelium as well. This sets in motion a cascade of events that drives clot formation and inflammation—two defining features of severe SARS-CoV-2 infection.
Pathology and autopsy studies have found particles of SARS-CoV-2 inside endothelial cells, and a growing body of evidence suggests that the endothelium plays a key role in the disease. In the early days of the pandemic, doctors discovered that damage to the endothelial lining in the lungs was associated with the fluid leakage and acute respiratory distress syndrome. Following this, researchers linked blood clots in the lungs and elsewhere to endothelial injury, and studies found viral particles in endothelial cells in organs other than the lungs, such as the kidneys. Thus, damage to the endothelium and the ensuing clotting and inflammation emerged as potential drivers of the strokes, cardiac injury, kidney disease, and other features of the disease.
Researchers have come to view the vasculature as the tissue most vulnerable to damage from SARS-CoV-2 infection.
“The protean manifestations of COVID-19 strongly implicate activation and dysfunction of the endothelium” as a unifying consequence of infection, “which can help us frame our thinking about the disease [mechanism],” says Peter Libby, a cardiovascular specialist at Harvard Medical School who has been studying the endothelium for nearly 40 years. He adds that this hypothesis “helps [us] understand why this disease so perniciously affects so many different organ systems.”
This hypothesis has been primarily based on clinical observations. Lee’s finding of high VWF levels and another study from Western University’s Douglas Fraser offer the best mechanistic evidence. Fraser and his colleagues tracked endothelial markers in 10 ICU patients with COVID-19, 10 ICU patients who were hospitalized for other reasons, and 10 healthy controls. The team found results similar to Lee’s investigation, such as raised plasma VWF and soluble P-selectin levels. In addition, Fraser and his colleagues noted telltale signs of damage to the glycocalyx, a moss-like molecular coating that envelops the endothelium, in COVID-19 patients.
Aaron Petrey, an immunologist and glycobiologist at the University of Utah School of Medicine, says that glycocalyx degradation and shedding is a theme in sepsis—which can occur in COVID-19—so “it’s unclear if this is a unique feature of COVID-19.”
Wagner, who has studied the endothelium for close to 40 years, tells The Scientist that both studies are a very good beginning to studying the endothelium in COVID-19. She says the finding that VWF is majorly increased is particularly noteworthy. “That, I think, is super important” to the increased tendency for clotting seen in COVID-19 patients.
Fraser, who published the results in August, says keeping close watch on endothelial cell markers and glycocalyx degradation could aid doctors in treating COVID-19 patients, alerting them to when it’s time to deploy medical interventions such as ventilators. Libby adds that these endothelial indicators also give doctors tools to assess which patients are likely to develop a blood clot and therefore should be treated with appropriate medications, such as blood thinners.
A few other reports from France, Germany, and China that have looked at various markers of endothelial and glycocalyx damage, both in vitro and in vivo, link endothelial damage to the severity of disease. All these studies bear witness to the endothelial cell dysfunction of COVID-19.
Lüscher, who was not involved in any of these studies, says these interrogations of the endothelium “are stimulating, but they are not solving the problem yet. What’s the first step that initiates this cascade of events? That’s the real question—that hasn’t been solved yet.”
Endothelium-directed therapies in COVID-19
A motley of studies are looking at ways to restore endothelial integrity in COVID-19 patients using various agents, including P-selectin blockers. Targeting the complement cascade—an inflammatory pathway that causes endothelial dysfunction—is another approach in clinical testing, with one exploratory Phase 2 trial recently attesting to the safety and tolerability of anti-complement therapy and reporting early efficacy signals.
Breaking up strings of VWF is yet another tactic that might work, says Wagner. As endothelial cells release abundant amounts of VWF, the molecules can self-associate and clog small blood vessels, but an enzyme present in plasma called ADAMTS13 chops up clusters of VWF. In COVID-19, ADAMTS13 levels plummet and, along with extremely high VWF levels, portends severe disease. It’s “a recipe for trouble,” says Wagner. “I believe that supplying ADAMTS13 to COVID-19 patients with high VWF would significantly reduce thrombosis and organ damage.” Currently, recombinant ADAMTS13 is being trialled in thrombotic thrombocytopenic purpura, a condition where ADAMTS13 deficiency leads to excess VWF and minute clots form in small blood vessels, but so far is not being tested in COVID-19 patients.
Christian Con Yost, a pediatrician at the University of Utah School of Medicine, tells The Scientist that breaking down these large VWF aggregates might also tame the downstream inflammation and accumulation of platelets and leukocytes. Lee agrees that the VWF/ADAMTS13 axis is worth further investigation. “We’re looking at this very closely,” he says.
Targeting these pathways in isolation may ameliorate disease severity but is unlikely to completely attenuate disease progression. —Jamie O’Sullivan, Royal College of Surgeons in Ireland
Lüscher, Libby, and other endothelial experts assert that targeting the two primary pathways to which the endothelium is intricately linked—hyperinflammation and clotting—would be the most beneficial. Reflecting on the current status of these two types of therapies, Libby says that the clinical research field is still in the era of non-randomized observational data and that outcomes of randomized placebo-controlled trials are desperately needed.
“It’s interesting to try this but I’m not sure that [it] will be sufficient to change the course of the disease,” Lüscher says of these diverse approaches to address endothelial mayhem. “This is not a very specific infection. There are many pathways. That’s the dilemma.”
Jamie O’Sullivan, a vascular biologist at the Royal College of Surgeons in Ireland, explains to The Scientist in an email: “Targeting these pathways in isolation may ameliorate disease severity but is unlikely to completely attenuate disease progression.”


thescientist--2020-11-03--New Developments in Live-Cell Analysis

New Developments in Live-Cell Analysis

Cell analysis has advanced at unprecedented rates , allowing scientists to understand signaling pathways at great depth .
Researchers in @ @ @ @ @ , and immunotherapy use cell analysis to understand disease mechanisms and to design safe and @ @ @ @ @ researchers , cell analysis technology that provides multiparametric and data-rich information is imperative .
Download @ @ @ @ @ to discover • How a single instrument combines live-cell imaging and real-time cell analysis to @ @ @ @ @ to perform live-cell imaging and real-time kinetic measurements on the same cell populations in a @ @ @ @ @ , days , or weeks without missing a data point

Cell analysis has advanced at unprecedented rates, allowing scientists to understand signaling pathways at great depth. Researchers in regenerative medicine, gene therapy, and immunotherapy use cell analysis to understand disease mechanisms and to design safe and effective therapies. For these researchers, cell analysis technology that provides multiparametric and data-rich information is imperative.
Download this ebook from Agilent Technologies to discover


thescientist--2020-11-01--Slingshot Spiders Pull More Gs than Cheetahs Do

ABOVE : A slingshot spider prepares to launch its cone-shaped web at a flying insect .
To do so , the spider will release a bundle of silk , catapulting both the spider and the web .
LAWRENCE E. REEVES Leg over leg , a furry brownish-black spider tugs on a single silk thread , tightening the frame of its web .
It pulls and pulls , as if removing slack from a slingshot , and then it waits .
Minutes pass , sometimes hours .
Then , when an unsuspecting insect flies by , the spider releases the thread @ @ @ @ @ @ @ web toward its prey .
All of this happens in the blink of an eye , with the spider and its web hurtling through the air at more than 4 meters per second ( 9 miles per hour ) with accelerations exceeding 130 g. That ’ s 130 times the acceleration experienced in freefall , and an order of magnitude greater than that of a sprinting cheetah .
Those eye-watering numbers led Georgia Tech chemical engineer Saad Bhamla to wonder : How the heck are these tiny spiders achieving such fast movements ?
@ @ @ @ @ @ @ with ultra-fast motions in biology , ” he says , so when he spotted one of these spiders flying past his face a few years ago while he was hiking through the Peruvian rainforest , he knew he had to investigate .
He checked the literature and found only a few papers on Theridiosomatidae , the arachnid family comprising spider species that use their webs as slingshots .
The papers were decades old and only described the slingshot motion , not the speeds or g-forces the spiders experienced .
So Bhamla enlisted the @ @ @ @ @ @ @ , and together they “ went out hunting for spiders in the Amazon rainforest , ” Alexander says .
After locating one of the spiders , which measure roughly 2 millimeters in length , the researchers would set up portable high-speed cameras with magnifying lenses to zoom in on and record their motions .
Then , either Alexander or Bhamla would snap their fingers to get the spider to catapult itself through the air .
Only later did the pair learn that a human finger-snap closely matches the frequency of a buzzing mosquito—and @ @ @ @ @ @ @ that set the spiders ’ spring off .
“ It ’ s just amazing that we can snap our fingers and get this magical thing , ” Bhamla says .
Analyzing the footage , Alexander and Bhamla could watch exactly how the spiders oriented themselves on the tension line at the front of their webs .
Facing away from the web , the spider grips its silk net with its four back legs and pulls itself up the tension line with its four front legs , bundling it up in two front appendages @ @ @ @ @ @ @ sensing the sounds of prey nearby-—most likely via its web , which appears to act like a small antenna—the spider releases the tension line .
Although researchers had previously assumed it let go of the silk thread altogether , Alexander and Bhamla ’ s videos show that the spider in fact only releases some of the line while keeping hold of a part of it with its pedipalps , making it easier to reset its slingshot to trap its next victim .
Again and again , the spider captures an insect , wraps @ @ @ @ @ @ @ “ comes right back to that tension line and bundles it up again .
That allows it to reset and reload pretty quickly , ” Alexander says .
The spider can usually slingshot itself several times before the web is destroyed .
The speeds and accelerations of this spider are impressive , but so is the fact that , unlike most web-building spiders , it ’ s actively hunting , Bhamla says .
“ It ’ s changed the function of its web , ” he says .
“ Instead of waiting for @ @ @ @ @ @ @ spider is going after things .
.
.
actually catching flying insects in midair.
” To see the video of this little spider pull on its line , load its web , sense its prey , and then fly through the air to trap it is humbling , says Sheila Patek , a biologist at Duke University who studies tiny spring mechanisms across the natural world but was not involved in this work .
“ We humans always think we ’ re the best at everything , and in the natural world , @ @ @ @ @ @ @ s pretty difficult.
” Other critters , including trap-jaw spiders and mantis shrimp , can move certain appendages such as claws or mouthparts at speeds of 30 to 80 kilometers per hour ( 20 to 50 miles per hour ) , she says .
But slingshot spiders are using an external tool , a web , to snare their prey , and they ’ re working at speeds faster than their nervous systems can monitor , so they have to plan ahead and essentially let their spring and latch system control what happens @ @ @ @ @ @ @ thread .
“ It ’ s superpower-type stuff , ” Patek says .
Theridiosomatidae aren ’ t completely unique in this respect , however .
Spiders in the Hyptiotes genus also use orb webs to actively hunt .
Hyptiotes spiders move at slower accelerations—a mere 772.85 m/s2 , compared with the Theridiosomatidae ’ s 1300 m/s2—yet they load energy in their webs similarly , then rocket toward prey , unleashing additional silk threads onto their victims to finalize the capture .
When the spider stops itself suddenly by clamping down on its tension @ @ @ @ @ @ @ jerk on the web wraps the capture threads around its prey from all directions .
What ’ s fascinating is the amount of energy the spiders can store in their web and then unleash to catch their prey , says Sarah Han , a graduate student in biologist Todd Blackledge ’ s lab at the University of Akron .
With Blackledge , she wants to investigate how the webbing material , typically thought to disperse energy , can , in fact , store energy , a characteristic that might inform the design of @ @ @ @ @ @ @ collaborating with Alexander , who will be starting her own lab at Auburn University in 2021 , and Bhamla on Theridiosomatidae , to look at how those spiders have evolved their slingshot systems .
Now that high-speed camera footage can offer scientists a frame-by-frame view of what the arachnids are doing , Patek says , “ it just opens up a myriad of areas of research in evolution , neuroscience , materials science , and human engineering .
”

ABOVE: A slingshot spider prepares to launch its cone-shaped web at a flying insect. To do so, the spider will release a bundle of silk, catapulting both the spider and the web.
LAWRENCE E. REEVES
Leg over leg, a furry brownish-black spider tugs on a single silk thread, tightening the frame of its web. It pulls and pulls, as if removing slack from a slingshot, and then it waits. Minutes pass, sometimes hours. Then, when an unsuspecting insect flies by, the spider releases the thread, springing itself and its satellite dish–shaped web toward its prey. All of this happens in the blink of an eye, with the spider and its web hurtling through the air at more than 4 meters per second (9 miles per hour) with accelerations exceeding 130 g. That’s 130 times the acceleration experienced in freefall, and an order of magnitude greater than that of a sprinting cheetah.
The spider can usually slingshot itself several times before the web is destroyed.
Those eye-watering numbers led Georgia Tech chemical engineer Saad Bhamla to wonder: How the heck are these tiny spiders achieving such fast movements? Bhamla’s lab is “obsessed with ultra-fast motions in biology,” he says, so when he spotted one of these spiders flying past his face a few years ago while he was hiking through the Peruvian rainforest, he knew he had to investigate. He checked the literature and found only a few papers on Theridiosomatidae, the arachnid family comprising spider species that use their webs as slingshots. The papers were decades old and only described the slingshot motion, not the speeds or g-forces the spiders experienced. So Bhamla enlisted the help of his postdoc, Symone Alexander, and together they “went out hunting for spiders in the Amazon rainforest,” Alexander says.
After locating one of the spiders, which measure roughly 2 millimeters in length, the researchers would set up portable high-speed cameras with magnifying lenses to zoom in on and record their motions. Then, either Alexander or Bhamla would snap their fingers to get the spider to catapult itself through the air. Only later did the pair learn that a human finger-snap closely matches the frequency of a buzzing mosquito—and that seemed to be the only frequency that set the spiders’ spring off. “It’s just amazing that we can snap our fingers and get this magical thing,” Bhamla says.
ANDRZEJ KRAUZE
Analyzing the footage, Alexander and Bhamla could watch exactly how the spiders oriented themselves on the tension line at the front of their webs. Facing away from the web, the spider grips its silk net with its four back legs and pulls itself up the tension line with its four front legs, bundling it up in two front appendages called pedipalps as it goes. On sensing the sounds of prey nearby-—most likely via its web, which appears to act like a small antenna—the spider releases the tension line. Although researchers had previously assumed it let go of the silk thread altogether, Alexander and Bhamla’s videos show that the spider in fact only releases some of the line while keeping hold of a part of it with its pedipalps, making it easier to reset its slingshot to trap its next victim. Again and again, the spider captures an insect, wraps it in silk for later, then “comes right back to that tension line and bundles it up again. That allows it to reset and reload pretty quickly,” Alexander says. The spider can usually slingshot itself several times before the web is destroyed.
The speeds and accelerations of this spider are impressive, but so is the fact that, unlike most web-building spiders, it’s actively hunting, Bhamla says. “It’s changed the function of its web,” he says. “Instead of waiting for something to collide with it, the spider is going after things . . . actually catching flying insects in midair.”
SETTING UP: Chemical engineer Saad Bhamla (left), postdoctoral researcher Symone Alexander (center), and Peruvian field guide Jaime Navarro adjust an ultrafast camera in preparation for imaging a slingshot spider. GEOFF GALLICE
To see the video of this little spider pull on its line, load its web, sense its prey, and then fly through the air to trap it is humbling, says Sheila Patek, a biologist at Duke University who studies tiny spring mechanisms across the natural world but was not involved in this work. “We humans always think we’re the best at everything, and in the natural world, those spiders are doing something that’s pretty difficult.” Other critters, including trap-jaw spiders and mantis shrimp, can move certain appendages such as claws or mouthparts at speeds of 30 to 80 kilometers per hour (20 to 50 miles per hour), she says. But slingshot spiders are using an external tool, a web, to snare their prey, and they’re working at speeds faster than their nervous systems can monitor, so they have to plan ahead and essentially let their spring and latch system control what happens after they let go of the tension thread. “It’s superpower-type stuff,” Patek says.
Instead of waiting for something to collide with it, the spider is going after things . . . actually catching flying insects in midair. —Saad Bhamla, Georgia Tech
Theridiosomatidae aren’t completely unique in this respect, however. Spiders in the Hyptiotes genus also use orb webs to actively hunt. Hyptiotes spiders move at slower accelerations—a mere 772.85 m/s2, compared with the Theridiosomatidae’s 1300 m/s2—yet they load energy in their webs similarly, then rocket toward prey, unleashing additional silk threads onto their victims to finalize the capture. When the spider stops itself suddenly by clamping down on its tension thread with its legs, the resulting jerk on the web wraps the capture threads around its prey from all directions.
What’s fascinating is the amount of energy the spiders can store in their web and then unleash to catch their prey, says Sarah Han, a graduate student in biologist Todd Blackledge’s lab at the University of Akron. With Blackledge, she wants to investigate how the webbing material, typically thought to disperse energy, can, in fact, store energy, a characteristic that might inform the design of synthetic silk. Han also recently began collaborating with Alexander, who will be starting her own lab at Auburn University in 2021, and Bhamla on Theridiosomatidae, to look at how those spiders have evolved their slingshot systems. Now that high-speed camera footage can offer scientists a frame-by-frame view of what the arachnids are doing, Patek says, “it just opens up a myriad of areas of research in evolution, neuroscience, materials science, and human engineering.”