CSHL's COVID/SARS CoV2 Rapid Research Meeting Reports II

Brianna Bibel, CSHL School of Biological Sciences

The COVID/SARS CoV2 Rapid Research Reports is a series of meetings organized by Cold Spring Harbor Laboratory (CSHL) that brings together scientists from around the world to discuss the very latest research on the novel coronavirus SARS-CoV-2 and the disease it causes, COVID-19. The series began in June 2020 and continues with the fifth installment this week.

Brianna “Bri” Bibel is a fifth-year graduate student in the CSHL School of Biological Sciences studying biochemistry and structural biology in Leemor Joshua-Tor’s lab. Bri is the scientist behind the popular blog, The Bumbling Biochemist and Instagram account @thebumblingbiochemist. Her style of explaining basic biochemical experiments is approachable, and appreciated by science teachers and young students alike. Here she guest writes for us, reflecting on the first three installments of the CSHL COVID meeting series.

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The second COVID/SARS CoV2 Rapid Research Reports meeting, held (virtually) July 21-22, 2020 was enlightening, but also a reminder of how much there is still to learn, and a lesson in “why things are so complicated.” At the first meeting, we got the basics down, and at this second meeting, scientists starting packing in the nuances and details they were finding as they dove deeper into the biology of this trickster of a virus. We got to hear from scientists approaching SARS-CoV-2 biology from different angles and quickly came to appreciate that it’s unique, that context (cell type, organ, etc.) really matters when doing experiments, and that various techniques used by different researchers can all contribute to our understanding. Here’s some of what we learned.

Lessons from other coronaviruses

If you mention “the coronavirus” these days, people assume you’re talking about SARS-CoV-2. However, there are a number of other coronaviruses. For example, there are four common-cold-causing coronaviruses as well as a couple of other really nasty ones – SARS-CoV (the original) and MERS (Middle Eastern Respiratory Syndrome).

Susanna Lau, University of Hong Kong

Of course, those are just the human-infecting coronaviruses. Additionally, there are lots of coronaviruses hanging out in other animals. We heard a talk by Susanna Lau of the University of Hong Kong on the role bats played in harboring the ancestors of SARS-CoV-2. Often bats don’t experience serious illness from the viruses thanks to their unique immune systems. But other animals are more susceptible, including livestock; Carolyn Machamer of John Hopkins University spoke about Infectious Bronchitis Virus (IBV) which infects birds and sometimes threatens the poultry industry. Researchers have been studying these coronaviruses for years (though with much greater difficulty securing funding) and have found a lot of shared features. In a roundtable discussion led by Susan Weiss of the University of Pennsylvania Perelman School of Medicine, some of the world’s most prominent coronavirus experts (including Machamer, Alexander Gorbalenya of Leiden University, Carolyn Machamer of John Hopkins, Cornelia Bergmann of the Cleveland Clinic, Susan Baker of Loyola University, and Volker Thiel of University of Bern) discussed how our knowledge of other coronaviruses informs current research on SARS-CoV-2.

Much of this previous knowledge has been tremendously advantageous. For example: Since we know things about the largely conserved genetic architecture of coronaviruses, once scientists had the sequence of the viral genome, they could quickly figure out where the different genes were and what each did. This allowed them to do things like isolate the sequence encoding the Spike protein and use it to develop a vaccine. Last meeting we heard from a scientist from Moderna about how this allowed them to so quickly get a vaccine candidate into testing. In this meeting, we heard a talk from Kizzmekia Corbett on how her group at the NIH is developing a platform to be able to take the genetic information from any emerging virus and use it to rapidly create a vaccine. This will hopefully prevent us from getting caught off-guard in the future.

“...quantity isn’t everything, and how well nAbs can bind and block the virus is also an important consideration. In fact, Hatziioannou found that the majority of patients produced some really strong binders, and she was able to isolate some of the strongest to test their therapeutic potential.”

Potential therapeutics

Multiple speakers at the meeting studied how the immune systems of patients reacted in the short term, immediately after infection, to determine which proteins might be targeted as part of potential therapies for COVID-19. Several presenters looked for antibodies, which are proteins produced by special immune cells (B cells) that can bind to specific regions (epitopes) of foreign things (antigens) such as viral proteins. If antibodies bind to a virus in such a way that the virus can no longer infect cells, we call it a “neutralizing antibody” or “nAb.” For SARS-CoV-2, nAbs often bind to the Spike protein and block it from binding to the ACE2 receptor. They have significant value both for the patient (as they can provide some protection against reinfection) as well as potential therapeutic use. Therefore, scientists are really interested in seeing if people make nAbs for SARS-CoV-2: If they do, and if we can isolate the B cells making the nAbs, we can potentially use those cells to make lots more.

Theodora Hatziioannou, The Rockefeller University

One of the scientists leading these efforts is Theodora Hatziioannou, an Associate Professor at The Rockefeller University in NY who’s been looking at the blood plasma (the cell-less part of blood) of recovered patients to test for nAbs. When analyzing data from hundreds of NY donors, what she found was really interesting: About 80% of recovered patients had detectable nAbs, but the distribution of antibody levels within those patients was highly skewed. Most patients had low levels of nAbs, but about 10% were “elite neutralizers,” churning out high levels of nAbs.

Don’t be scared off by her finding that most recovered patients only made small amounts of nAbs – quantity isn’t everything, and how well nAbs can bind and block the virus is also an important consideration. In fact, Hatziioannou found that the majority of patients produced some really strong binders, and she was able to isolate some of the strongest to test their therapeutic potential.

Every time the virus copies its genome (replicates) it can make little mistakes (mutations). Most mutations are harmless or even detrimental to the virus, but some give the virus beneficial properties under certain selective pressures, like the presence of antibodies. By growing the virus in the presence of different nAbs, Hatziioannou was able to select for viruses that had mutations in the gene for the Spike protein which allowed them to resist binding to the nAbs – a phenomenon called “viral escape.” When she sequenced the mutated Spike genes from those viruses, she found that resistance to different nAbs clustered to mutations in different specific locations on Spike. She then looked at the sequences of the Spike gene from patient samples and found that, although rare, some indeed had mutations in those regions which would likely make them resistant to individual nAbs. So, if you were to try to treat one of those patients with that nAb, they likely wouldn’t respond. However, Hatziioannou also presented evidence that combinations of nAbs targeting different regions (epitopes) of Spike could prevent that viral escape, as it’s unlikely a virus will have a Spike that has multiple resistance-giving mutations. Therefore, she suggested that for treatment/prophylaxis, multiple nAbs be given as an “antibody cocktail.” Indeed, this is the strategy being taken by Regeneron.  

Of course, any nAb still has to be delivered, and this can be difficult and costly because human antibodies aren’t very stable. This has led some scientists to look to alternatives – like llamas! Gerald McInerney of the Karolinska Institute explained how alpacas have unique antibodies called nanobodies which are smaller, more stable, and easier to deliver than human antibodies. His group is working to engineer an alpaca nanobody with strong neutralizing ability and he showed us some of his latest results.

Even more molecular biology

Biochemistry/molecular biology is really my jam, so I was so happy that this meeting was jam-packed with it! I’m really interested in the mechanisms behind molecular marvels and, thankfully, a lot of top scientists are as well. But how do they figure out those processes? A common way to explore how the coronavirus gets into cells and what it does once inside is to test things out in cells in a dish. This is also a great way to screen potential drugs to see if they can prevent the virus from infecting cells and/or causing damage. But different cell types have different levels of various proteins and molecules, and thus might behave differently and give different results in experiments. It’s therefore crucial to do experiments in multiple types of cells and to be cautious with generalizations.

“...by doing experiments in different cell types and different model organisms, and by using different techniques to try to answer the same questions, we are able to study many different aspects of fundamental SARS-CoV-2 viral biology.”

Two cell lines commonly used for coronavirus research are Vero, derived from a monkey’s kidney, and Calu3, human respiratory cells. These lines are chosen in part because they both express the ACE2 receptor, which the coronavirus uses as a cellular docking station. The coronavirus Spike protein sticks out from the viral membrane and latches on to ACE2 to kickstart the viral fusion process. Viral fusion involves the Spike protein undergoing a shape-shift (conformational change) to merge its viral membrane with the cell membrane and dump its contents inside.

To undergo that conformational change, the Spike protein has to be cleaved in a couple of places by protein-cutting enzymes called proteases. As Fang Li from the University of Minnesota explained, there are many proteases capable of doing this, and different cell types express different ones. Further complicating things, some of these proteases, like TMPRSS2, are located at the cell’s plasma membrane (the membrane surrounding the cell) and thus can do the cutting at the cell surface, whereas other proteases are intracellular and can only cleave if the virus gets “swallowed” by the cell in a process called endocytosis. Figure 1 of this publication nicely illustrates this.

Vineet Menachery, The University of Texas Medical Branch

Processing of the virus will thus vary by cell type, as was demonstrated by The University of Texas Medical Branch (UTMB)’s Vineet Menachery. He looked at the importance of the “furin cleavage site,” which is a sequence in the SARS-CoV-2 Spike protein that allows one of the snips to be done by a “furin protein.” Menachery found that the importance of this site was greatly dependent on the cell type – mutating the sequence of the furin cleavage site increased the replication rate in Vero cells but hindered it in in Calu3 cells. Given the conflicting results, he turned to a hamster model, and was was able to share preliminary evidence that disrupting the furin site led to a weaker virus in this model.

Other researchers at the meeting also presented experimental results that differed based on the cell type or method. But this shouldn’t be discouraging or make you not trust science – instead, by doing experiments in different cell types and different model organisms, and by using different techniques to try to answer the same questions, we are able to study many different aspects of fundamental SARS-CoV-2 viral biology. If, like Menachery, scientists get different results in different cell lines, they see the results as the virus trying to tell us something. What is it about one cell type that makes it act differently from another cell type? Menachery, for example, took the conflicting results as evidence that there are potentially as-yet-unknown proteases present in Calu3 cells but not Vero cells that can affect SARS-CoV-2 processing. By looking into these factors, we can better understand the basic biology and potentially find novel therapeutic targets.

So yes, when it comes to SARS-CoV-2, things are complicated, but they’re definitely not hopeless! Years of research on other coronaviruses and the development of a variety of experimental methods have prepared us to face such complications head-on. And hopefully, work on SARS-CoV-2 will help us head off the next pandemic!

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This post is part of a series. Read a summary of the first CSHL COVID meting here, and here for a recap of the third meeting.

The next installment of the COVID/SARS CoV2 Rapid Research Reports series will take place on January 26-27, 2021.

CSHL's COVID/SARS CoV2 Rapid Research Meeting Reports I

Brianna Bibel, CSHL School of Biological Sciences

The COVID/SARS CoV2 Rapid Research Reports is a series of meetings organized by Cold Spring Harbor Laboratory (CSHL) that brings together scientists from around the world to discuss the very latest research on the novel coronavirus SARS-CoV-2 and the disease it causes, COVID-19. The series began in June 2020 and continues with the fifth installment this week.

Brianna “Bri” Bibel is a fifth-year graduate student in the CSHL School of Biological Sciences studying biochemistry and structural biology in Leemor Joshua-Tor’s lab. Bri is the scientist behind the popular blog, The Bumbling Biochemist and Instagram account @thebumblingbiochemist. Her style of explaining basic biochemical experiments is approachable, and appreciated by science teachers and young students alike. Here she guest writes for us, reflecting on the first three installments of the CSHL COVID meeting series.

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Do you remember where you were when you first heard about the novel coronavirus SARS-CoV-2? I do – vividly. I was at the gym and I saw a trending story on Twitter about a strange cluster of pneumonia cases in Wuhan, China. For the next couple of months I’d hear about it sporadically and then, wham! It was here. It was everywhere. And we had a lot of catching up to do.

So I was excited when I learned about a series of virtual meetings being set up by Cold Spring Harbor Laboratory (CSHL). Titled “COVID/SARS CoV2 Rapid Research Reports,” these meetings would feature experts from around the world filling us all in on the very latest research on the virus SARS-CoV-2 and the disease it causes, COVID-19. The first meeting was held June 16-17, 2020, and featured close to 30 talks. I don’t have space to go into every one of them, but I’d like to share some of the highlights.

A short history of coronavirus biology

Susan Weiss, University of Pennsylvania

The meeting was kicked off by a talk I know I needed – a lecture on the history and basic biology of coronaviruses by University of Pennsylvania’s Susan Weiss. Coronaviruses may have been new to many of us, but not to Weiss – SARS-Cov-2 was, of course, but Weiss has years of experience working on other, related, coronaviruses, so was well positioned to get us all up to speed. She told us about how coronaviruses have a single-stranded RNA genome that, although very small compared to our genome, is able to pack in a lot of tools to efficiently hijack our cells and bodies. For example, it makes an RNA-dependent RNA polymerase that it uses to make more copies of its RNA. Some of the copies it makes are full-length copies, which it can package up and ship out to infect more cells, whereas others are shorter “subgenomic” copies that it can use to make proteins from.

Some of these proteins are ones you’ve probably heard a lot about, such as the Spike protein, the protein that juts out from the viral membrane like a crown or halo, giving coronaviruses their name and giving them a way to dock onto our cells by binding to cellular receptors (a membrane protein called ACE2 in the case of SARS-CoV-2). But what fascinated me the most were the “Nsps” (non-structural proteins) she told us about that I’d never heard of. They don’t get that much attention, but many of them have the job of making sure our bodies don’t pay the virus much attention! For example, nsp13, nsp14 & nsp16 help with capping the viral RNAs so that they look like our own RNAs and thus don’t trigger an interferon-mediated immune response.

“When confronted with something “foreign,” an animal’s immune system has to decide what to do about it and how “paranoid” to be. Instead of focusing on host defense...bats err on the side of tolerance.”

Bats as reservoirs

Speaking of immune response, next up we heard from Linfa Wang from the University of Singapore about how bats are able to serve as reservoirs for viruses like SARS-CoV-2 because they have better balanced immune responses than us. When confronted with something “foreign,” an animal’s immune system has to decide what to do about it and how “paranoid” to be. Instead of focusing on host defense, which risks potentially over-reacting and causing autoimmune-related disorders and/or excessive inflammation, bats err on the side of tolerance. Wang explained his work showing that bats actually have a different way to control inflammation than other mammals, so they’re able to harbor viruses and allow those viruses to replicate within their bodies (and potentially go on to infect others) without getting sick themselves. Consistent with Wang’s findings, the University of Hong Kong’s Leo Poon told us that, since 2005 when he discovered the first bat coronavirus, he, and other labs around the world, have found many, many more (including ones closely related to SARS-CoV-2), stressing the importance of continuous surveillance in case they develop the capacity to infect other species.

Spike proteins

Figure 5 from Model for structural rearrangements of SARS-Cov-2 S protein. Image source.

As a graduate student in a structural biology lab, I know I’m biased, but some of my favorite talks came during the “molecular biology” session, where we got to hear about early work solving the structure of the coronavirus Spike protein. This protein is a bit like a molecular Transformer; after docking to ACE2 receptors on cell surfaces and getting cleaved by protease(s), it’s able to undergo a dramatic conformational change that enables it to fuse the viral membrane with the cell membrane, thereby releasing the viral genome into our cells.

I remember how surprised I was when the first SARS-CoV-2 Spike structure was published so quickly back in March, and at the meeting I got to learn more about how that was possible. Similar to Weiss, Jason McLellan from the University of Texas had a history of work on other coronaviruses – he had already solved the structures of the Spike proteins from SARS-CoV and MERS. So as soon as he received the sequence for the Spike protein, he cloned it and stuck it into cells to have them make Spike protein he could purify and take “molecular pictures” of. Thanks to his prior work on the “original” SARS-CoV & MERS Spike proteins, he knew that this Spike likely wouldn’t want to sit still for its photo-op. But he also knew a couple of changes he could make to the protein to help stabilize it in the pre-fusion conformation. By switching out a couple of amino acids (protein letters) in part of the protein, he was able to “freeze” it and then literally freeze it in a thin sea of vitreous ice (glasslike water) and use cryo-electron microscopy to solve its structure.

Overall, McLellan found that it looked very similar to the SARS-CoV Spike protein, but he was able to identify key differences in the part of the Spike responsible for binding the ACE2 receptor (the receptor binding domain). The structure was great, but McClellan and his lab weren’t satisfied – there were missing regions in their model and they were getting poor expression of their original construct, so McClellan told us about ongoing work in his lab trying to engineer a more stable, better-expressing version.

Neutralizing antibodies

David Veesler, University of Washington

One of the reasons it’s so valuable to know the structure of the SARS-CoV-2 Spike protein is because pre-fusion Spike can be used to look for neutralizing antibodies, as we got to hear about in a talk by David Veesler of the University of Washington. Antibodies are small proteins made by the immune system that bind specifically to foreign molecules (aka antigens) such as viral proteins; neutralizing antibodies are a subclass of antibodies that bind to a virus in such a way that they prevent the virus from infecting cells, thus “neutralizing” their threat. The search for neutralizing antibodies for SARS-CoV-2 has been focused on the Spike protein because, if antibodies bind to the Spike protein in the right places, they can prevent it from binding ACE2 and/or undergoing fusion, and thus prevent the virus from getting in.

Veesler developed a pseudovirus assay he could use to test for neutralizing antibodies. In these experiments, he used a different virus, MLV, to make “fake” SARS-CoV-2 viral particles that express the SARS-CoV-2 Spike protein and a fluorescence reporter, and then added this pseudovirus to cells. If the virus can infect cells, those cells will start glowing. But if the virus can’t get in because neutralizing antibodies are present, the cells won’t glow. Veesler and his collaborators used this assay to look for antibodies in the blood of SARS patients, hoping to find cross-reactive neutralizing antibodies (thanks to the high similarity between the Spike proteins of SARS and SARS-CoV-2). And they found some – Veesler used cryo-EM to solve the structure of one of them bound to SARS-CoV-2, and is now taking it into clinical development for use as a therapeutic.

“...if you use multiple antibodies you can prevent “viral escape,” a scenario whereby rare mutations in the Spike protein prevent the antibody from binding and therefore allow the virus in. ”

Later in the meeting we heard from Christos Kyratsous from Regeneron Pharmaceuticals about their development of neutralizing monoclonal antibody cocktails. Kyratsous explained that if you use multiple antibodies you can prevent “viral escape,” a scenario whereby rare mutations in the Spike protein prevent the antibody from binding and therefore allow the virus in. While some versions of the virus might have one of those mutations, it’s much less likely that a virus would have mutations that prevent binding of both antibodies. To find the antibodies to put in their cocktail, Kyratsous and his team immunized mice which had been genetically altered to produce human antibodies, and screened the mice’s blood along with blood from patients who had recovered from COVID-19 for the presence of neutralizing antibodies, choosing the most promising ones to take into clinical development. Kyratsous’ talk came just days after Regeneron had announced their first clinical trial, so it was especially exciting to hear about.

Antivirals and vaccines

Last but definitely not least was the session on “Antivirals and Vaccines,” where talks featured experts from Moderna and Gilead (among others), companies I’d heard so much about in the news but mostly in soundbytes and short pieces aimed at a more general audience. Here I got to hear about the science of Moderna’s mRNA vaccine and Gilead’s RNA dependent RNA polymerase (RdRp) inhibitor remdesivir, at a deeper, geekier, level.

Remdesivir is a nucleotide analog – essentially a “fake” RNA letter that the viral RdRp gets tricked into using, resulting in RdRp getting stuck and being unable to successfully copy the viral RNA. As we heard from Gilead’s Danielle Porter, it’s actually a repurposed drug. It was initially found by Gilead in a screen for hepatitis C drugs, and was later provided to the CDC and U.S. Army Medical Research Institute of Infectious Diseases as part of a library of molecules the government agencies could screen for effectiveness against various infectious diseases. The government scientists found it potentially useful against Ebola, but it was put aside after a different treatment (monoclonal antibodies) worked better. Since remdesivir had the potential to target viruses that depend on viral RdRps, scientists tested it against SARS-CoV-2 and got some promising early results that led to larger clinical trials. Because Gilead had already taken remdesivir fairly far along in the testing process for the Ebola trials, scientists knew a lot about its safety profile - and they knew how to make it – enabling it to come to market quickly.

Matthew Hall, National Center for Advancing Translational Sciences

The story of remdesivir highlights the potential of drug repurposing and, if there are other existing drugs that could be repurposed to treat COVID-19, Matthew Hall wants to find them! He told us how he and his team at the NIH are running high-throughput screens of various SARS-CoV-2-related assays against all approved drugs, and sharing the data freely through their OpenData Portal, which they also use to host data from similar assays run around the world, allowing for the most people possible to benefit.   

This meeting was an amazing opportunity, especially as a graduate student. I got to hear directly from the scientists whose names graced the papers I’d been poring over as I tried to make sense of what was going on. If I had to sum up the spirit of the first meeting in one word, it’d be “unity.” Despite the fact that we were coming from all over the world, despite the fact that attendees were of all training levels and most of us were completely outside of the virology field, there was a strong sense that we were all in this together. That those with the knowledge were willing to share it freely, with unprecedented speed and scale. That labs from different institutions and even different countries were teaming up in the fight. Coming away from the meeting, not only did I have hope about tackling the disease, but I also had hope that the future of science – all science – will be much more collaborative and open.

“Despite the fact that we were coming from all over the world, despite the fact that attendees were of all training levels and most of us were completely outside of the virology field, there was a strong sense that we were all in this together.”

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This post is part of a series. Go here for a recap of the second COVID meeting, and here for the third meeting.

The next installment of the COVID/SARS CoV2 Rapid Research Reports series will take place on January 26-27, 2021.

Visitor of the Week: Yi Fei Lee

Meet Yi Fei Lee of the Genome Institute of Singapore within the Agency for Science, Technology and Research! The PhD student is a member of the Laboratory of Translational Cancer Biology led by Dr. Tam Wai Leong. She spent most of this week with us at The PARP Family & ADP-ribosylation virtual meeting. This is Yi Fei’s first meeting at CSHL!

Tell us about your research.
The molecular profiles of lung adenocarcinoma differ between ethnic groups, and we use sequencing data from one of the largest Asian clinical cohorts to predict new driver genes. I'm currently working on understanding the mechanisms underlying how these genes drive cancer formation or progression, as well as how we might be able to therapeutically exploit them.

How did you decide to focus on this area/project?
I've always been interested in cancer research because it is such a prevalent healthcare problem, and also an intriguing intellectual one to tackle. Cancer cells are diverse and able to grow and rewire themselves rapidly, presenting new therapeutic vulnerabilities yet also conferring resistance to existing therapies - it's almost like a cat and mouse game. Lung cancer is the leading cause of cancer mortality so I hope that incremental findings in this field could lead to better clinical outcomes.  

What and/or who is the inspiration behind your scientific journey?
I have always had an interest in the sciences so it was only a natural extension to try out research. During my undergraduate days, I interned at different labs and was fortunate to have had inspiring mentors who helped me to grow as a scientist and shape my research interests. The potential in uncovering new knowledge that could be used to meet currently unmet needs also keeps me motivated.

What impact do you hope to make through your work?
I hope to be able to identify novel biomarkers or drug targets that can enable better stratification of patients for more effective treatments. I would love for my work to be able to add value to the field and contribute to improving therapeutic outcomes. 

What do you love most about being a researcher?
I like tinkering around in the lab and being curious, so designing and carrying out experiments to test my hypotheses has always been an enjoyable process. I’m also thankful for the collaborative and supportive environment and love bouncing ideas off colleagues.

What drew you to attend this meeting?
Through my research, I came across a PARP protein and realized there is so much to learn about this fascinating family of proteins! I felt that this meeting would be a good platform to interact with and understand the work of other researchers in the field.

What is your key takeaway from the Meeting; and how do you plan to apply it to your work?
The meeting gave me new insight into the balance and cross-talk between ADP-ribosylation and other post-translational modifications such as phosphorylation, and how that in turn regulates protein activity. I will be using these new ideas to relook at my data from different angles and plan some new experiments.

What feedback or advice would you share with someone considering to participate in this meeting?
Although meetings are inevitably in virtual format these days, a lot of care and thought has gone into creating channels for discussion and interaction between the participants, and I find this to be very valuable. I actually also liked that I could take my time to look at the posters on the virtual platform – there are so many interesting and informative ones! I’m enjoying my first CSHL meeting and my advice would be to make use of the available platforms to engage with other participants.

What’s the most memorable thing that happened during the Meeting?
The meeting is still in progress, but one of the most memorable moments for me thus far has been the Meet the Speakers session where I got to chat with the speakers – Drs. Lee Kraus and Anthony Leung. I was able to gain a sense of how the field has evolved and what other exciting pursuits lie ahead. I also enjoyed learning about the research interests of other trainees in a more informal setting, and this definitely added a more personal touch to the virtual format of the meeting. 

Thank you to Yi Fei for being this week's featured visitor. To meet other featured researchers - and discover the wide range of science that takes part in a CSHL meeting or course - go here.

Visitor of the Week: Gemma Camara

Meet Gemma Camara of the Bishop’s University in Quebec, Canada! The undergraduate student is completing her research studies under a second experiential learning course at Dr. Rona Graham’s lab at Sherbrooke University, that is co-supervised by Bishop’s University Psychology Department Chairperson Dr. Jonathan Carriere. She spent most of this week with us at the 2020 Neurodegenerative Diseases: Biology & Therapeutics virtual meeting where she presented her first-ever poster entitled “The relationship between cognitive scores and detection of specific odours in the elderly”.

 Tell us about your research.
Olfactory dysfunction is important as it is a common early sign of neurodegeneration. My research project looks at three important questions:

1. If seniors experience general loss or loss of specific scents,

2. The difference in scent identification abilities between males and females,

3. If there is a relationship between correct scent identification and cognitive test scores.

How did you decide to focus on this area/project?
I started studying under Dr. Graham in her lab during the winter of 2020 with the co-supervision of Dr. Adrianna Mendrek at Bishop's University. Throughout this research experience, I’ve discovered a passion for olfactory function by working on Dr. Graham's research.

What and/or who is the inspiration behind your scientific journey?
I always had a passion for health science. Bishop's University piqued my interest because it is an English University with smaller classes, which is not easy to find in Quebec. The field of Neuroscience spoke to me; I love the professors and opportunities that this program provides. It is the reason I am here today. Students get a tremendous amount of support to pursue whatever they desire.  

What impact do you hope to make through your work?
Many elderly do not self-report olfactory dysfunction because of its subtle change in daily life. If olfaction is related to cognitive decline and early-onset AD, we could prolong its function by introducing early interventions such as olfactory therapy.

Where do you see yourself in five years?
I see myself finishing my Ph.D. in five years, maybe even giving a TED Talk about my research. The subject will most likely be on the physiology of neural pathways and related to olfaction, but I am open to other issues. I am in my third and last year of undergrad for now, and there is still a lot of research to do in the field of olfactory dysfunction.

What do you love most about being a researcher?
The people and science! I love the fact that when you find another researcher who has a similar passion, two strangers can instantly connect and work together or give each other advice, suggestions, etc.

What drew you to attend this meeting?
My supervisor Dr. Graham had suggested this meeting. She is always looking to guide me through new opportunities that will allow me to grow and go beyond my comfort zone. I am very grateful to have such a good mentor.

What is your key takeaway from the Meeting; and how do you plan to apply it to your work?
During the first night’s social event when Dr. Aaron Gitler asked me if I had applied to Stanford. I never thought to push myself to be a part of any of the “Ivy Leagues” before but his question made me think about the limitations I've set for myself. The sky's the limit, and there are tons of great Universities looking to take on smart ambitious students who are hardworking and who put themselves out there. I plan to continue working hard as a researcher so that soon I’ll be giving a presentation on one of our “groundbreaking” findings.

Also, during the Meet the Speakers event, I had the opportunity to meet and chat with Dr. Fenghua Hu and Dr. Goncalo Castelo-Branco, who both gave fantastic presentations on the first day.

What feedback or advice would you share with someone considering to participate in this meeting?
Participate in as many of the conference activities as possible! Fully immersing myself has been a great experience. The speaker and poster presentations enable an opportunity for feedback on published and unpublished data. You will have so many great interactions with the participants!

What’s the most memorable thing that happened during the Meeting?
The conference is still not over! But so far, the most memorable moment for me was the icebreaker on the first day. I love conversing with researchers from different universities. Everyone is extremely approachable and eager to give and receive feedback on their work. Thus far, every presentation has been impressive; I would highlight the presentation by Dr. Chloe Lee-Lopez on Male sex chromosomes attenuate cytokine response to inflammation in aging brain.

Thank you to Gemma for being this week's featured visitor. To meet other featured researchers - and discover the wide range of science that takes part in a CSHL meeting or course - go here.

Image provided by Gemma Camara

Visitor of the Week: Erika Estrada

Meet Erika Estrada of the University of California, Davis! Erika is a PhD Student in Linda Harris’ lab who serendipitously “flew” into science. She took part in this week’s Advanced Sequencing Technologies & Bioinformatics Analysis virtual course – her first at CSHL. Erika shares her career plans and we look forward to her shepherding the next generation of scientists.

Tell us about your research.
My research focuses on enhancing microbial food safety with an emphasizing on produce, and tree nuts.

How did you decide to focus on this area/project?
Honestly, serendipity. While I was flying back from a conference, the person sitting next to me was working on a presentation. I peeked on his screen and saw pictures of microbes, soil and water samples. I asked him about his job, he was an extension faculty at UC Davis and he offered me a job in his lab. After just a couple days of working in his lab, I knew that I wanted to study foodborne pathogens for the rest of my life.

What and/or who is the inspiration behind your scientific journey?
My future students. In the near future, I would like to become a professor in hopes to inspire, mentor and guide students through their academic career. I hope my story can show them that if I did it (got a PhD and become a scientist) then so can they.

Erika receiving the Developing Scientist Award at the 2019 International Association of Food Protection (IAFP) Meeting.

Where do you see yourself in five years?
My ultimate career goal is to become an extension faculty and a professor for an academic institution. As an extension specialist, I want to generate, transmit, and apply knowledge for the direct benefit of the food industry, farmers, and my community. I hope that through my research I am able to develop practices that enhance produce food safety.

As a professor, I want to share my knowledge and academic journey with the younger generations, especially those from disadvantaged backgrounds, like myself, to motivate them to pursue careers in science.

What do you love most about being a researcher?

I think what I love most about being a researcher is that I get to study something that no one has studied before. I get to provide answers to questions that ultimately have a positive impact in my community, and the food industry.

What drew you to apply to this course?
Currently, I am working on a project aiming to do comparative genomic analysis of multiple Salmonella isolates obtained from a 3-year pistachio survey in California. The ultimate goal of this project is to understand the underlying reasons for unique microbial contamination profile in pistachios.  However, this is the first time during my academic career that I have to do use advanced Bioinformatics tools and techniques. During this quarantine, I have taken a couple of free online courses on UNIX, and read about different software that would be beneficial to process my sequences. Honestly, learning the basics of UNIX, NCBI databases, and data processing software using YouTube, online classes and different websites has been one of the most challenging and satisfying things I have done in my whole academic career. However, I believe that attending this course would be a valuable opportunity to obtain formalized training in the topic and to keep instilling my passion for learning about the application of sequencing technologies and bioinformatics analyses.

What feedback or advice would you share with someone considering to participate in this course?
Definitely try to get familiar with R and Unix so that you are able to truly focus on learning about the bioinformatics tools and technologies covered rather than focusing on understanding the code.

What’s the most memorable thing that happened during the Course?
I think the most memorable thing that happened during the course was learning about the power of R when we were building visual tool, such as graphs, plots and heat maps, to actually see the results of our analysis. After this course, I am committed to learn more about R.

Thank you to Erika for being this week's featured visitor. To meet other featured researchers - and discover the wide range of science that takes part in a CSHL meeting or course - go here.

Images provided by Erika Estrada