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Copyright: © Richard Jacobs
As the director of molecular visualization in the Department of Biological Chemistry and Molecular Pharmacology at Harvard Medical School, and the president and CEO of Digizyme, Gaël McGill is interested in how we understand complex science through images. In this episode, you will learn:
If you've ever watched a YouTube video on a process like DNA transcription, then you were likely viewing images generated from a software program—not a microscope. Which design decisions lead to effective imagery for communicating scientific concepts? How do you combine a ton of data into representations that help people understand complicated scientific principles and improve communication in science? How do you strike a balance between doing the science justice and making it simple enough to reach the understanding of students and laymen?
These are the questions that drive McGill's work, and just a few of the ones he discusses on today's episode. He emphasizes the pedagogical value of getting people to think about how certain images are made, as he believes that in and of itself is an excellent way to learn the material presented by the images. In this vein of thought, he shares the thought-provoking philosophy that "science is not a bunch of facts; science is a way of knowing, and it has to be taught that way."
McGill explains how techniques such as X-ray crystallography and cryo-electron microscopy can be used to reconstitute an image and obtain the information for the precise location of every single atom in a molecule—whether it's a small one like a hormone, or a large one like an entire virus.
Check out https://clarafi.com/ to browse animations selected and curated by the team at Digizyme and explore a series of online courses and training for those interested in scientific illustration.
Researcher Frederic Bard has studied coronaviruses' step-by-step entry and replication inside cells. He explains to listeners which stages are the most promising for interference. Along the way, he describes
Frederic Bard is an adjunct associate professor in the Department of Biochemistry at Yong Loo Lin School of Medicine at the National University of Singapore and is part of the Institute of Cellular and Molecular Biology with the Agency for Science, Technology, and Research (A Star) in Singapore. He explains to listeners about the importance of host genes for coronavirus replication. He reminds us that viruses are parasites and need the machinery of a cell to replicate—he has researched different proteins and machines inside the cell that help the structure of viruses to replicate: if we can understand that, he says, maybe we can block replication.
He describes the two moments that show the most promise for disturbing this process, namely when viruses bind with spike proteins on the outside of the cell and when they enter the cytosol for the viruses' RNA replication. A few years ago, he published work identifying the VCP protein that coronaviruses bind with and is now researching the possibility of inhibiting that protein without hurting the cell. That is part of the challenge, he explains—to make the cell a little bit sick to inhibit the virus replication but not enough to damage the cell and health of the person. Along the way, he explains cell mechanisms in response to viruses, how the structure of virus works with the endosomes and cytosol.
For more, see his lab websites with links to his publications and contact information: https://www.a-star.edu.sg/imcb/science/scientific-programmes/multi-modal-molecular-(m3)-biology and https://bch.nus.edu.sg/fredericbard.htm.
Researcher Nikita Ved is studying birth defects as a result of diabetes and wants to increase public awareness of these issues. She tells listeners
Nikita Ved is a Novo Nordisk Postdoctoral Research Fellow in Dr. Duncan Sparrow's group in the Department of Physiology, Anatomy and Genetics at the University of Oxford. She researches how diabetes during pregnancy causes birth defects in the embryo, most commonly heart issues; this includes all forms of diabetes, from the 2 types of diabetes more commonly known as well as gestational. She says that many people don't know that one of the major complications of diabetes happens during pregnancy. If fact, it can increase the rate of miscarriage and birth defects by up to 30%.
She explains how difficult it has been to educate the public about these concerns, perhaps because the focus of diabetic complications tends to center on worries about blindness, kidneys, and other neuropathy. Yet she feels that birth defects should be put on the same level of awareness. She describes some of the difficulty involved in these studies but also some protocols that aren't helping, such as not testing pregnant women for diabetes or gestational diabetes until their 2nd trimester while birth defects happen very early in the pregnancy. She advocates for screening for and educating patients about the 2 types of diabetes as they undergo regular gynecological checkups well before they are pregnant.
For more and for contact information, see her web page at the lab: https://www.dpag.ox.ac.uk/team/nikita-ved
Distinguished professor and Chair of the Department of Biology at the University of Alabama at Birmingham, Steven N. Austad, joins the podcast to discuss his research on the biology of ageing. Tune in to learn the following:
For over 30 years, Austad has been studying the biology of ageing. He more or less stumbled upon this area of research while conducting field work in South America on opossums; much to his surprise, he learned that the lifespan of these animals is very short—just 18 months on average—and as they age, they develop numerous ailments, including cataracts, muscle atrophy, and dental issues. This spurred Austad's interest in the topic of ageing and compelled him to research why certain species age at the rate they do, and more broadly, why ageing occurs at all.
Austad studies traditional lab animals and unusual animals in the field, such as small bats and Arctica islandica, a species of clam that can live for over 500 years. Despite the general trend of increased life expectancy with increased size, these small animals show a fascinating ability to age successfully—even against the rigors of the wild.
By studying the process of ageing in these animals, Austad believes that insights can be gained that might inform us on how to increase human longevity. He explains one of the suspected ways in which certain species of clams, including the Arctica islandica, live so long. The key lies at least partially in the ability to regulate and maintain proper protein folding. Indeed, it is the age-related weakened ability to do this that leads to dementia and other common features of ageing in humans. Currently, he's working on sequencing the genomes of various species of clams that live various lengths of time with the hope that this will reveal which molecules might be involved in the protein folding process.
Learn more about Austad's work by visiting https://www.stevenaustad.com/.
Ben Novak is the lead scientist at Revive & Restore, a leading wildlife conservation organization that promotes the incorporation of biotechnology in various conservation efforts. He joins the show to discuss some fascinating topics, including the following:
Novak joined the Revive & Restore team in early 2012 to work on the Passenger Pigeon Project. Since then, he's worked on a number of projects, including those involving the endangered black-footed ferret and endangered heath hens.
For over a century now, scientists have been restoring populations once they go extinct, but this hasn't been done for every vital extinct species, such as the woolly mammoth and Passenger Pigeon. This is where the team at Revive & Restore sees the greatest potential for new biotechnologies to enhance and improve conservation efforts.
Among these technologies are animal gene editing, embryogenesis, and primordial germ cell transfer. Novak says that reproductive technologies are needed in order for their current projects to succeed, and he explains how the Catalyst Science Fund program has begun employing reproductive techniques for use in poultry, but not in wildlife. To reach this end, they are beginning with a project on the greater prairie chicken, which was funded just last year and has remained unimpeded since.
Novak discusses the details of the various projects they're working on, how the prevention or reversal of species extinction could be accomplished with different biotechnologies, current restoration projects, and the many concerns and challenges encountered in this type of work.
Check out https://reviverestore.org/ to learn more.
As a research group leader at the Max Planck Institute for Biology of Ageing in Cologne, Germany, Dario Valenzano is trying to understand the molecular and genetic bases underlying differences between lifespans and ageing processes of different species, and how we might be able to manipulate our own. In this episode, you will learn:
Some species live for just a few hours, while others live for thousands of years. Why and how have species evolved such different lifespans, and how might the answer to these questions allow us to increase our own longevity and reduce the risk of many diseases? These questions form the cornerstone of the research being carried out by Valenzano and his group.
As a model organism for this research, the team is using the African turquoise killifish, which is the shortest-lived vertebrate known to exist. This fish lives approximately four months both in the lab and in its natural environment. In studying how this species evolved to be so short-lived, they have found that Darwinian selection has little to do with it; rather, Valenzano says its short lifespan came about as a mere accident. For this type of fish, there is little advantage to being long-lived, and without selective pressure to survive for a long time, selection doesn't act to remove deleterious mutations in late life. Valenzano explains what this might reveal about human evolution, and in particular, late-life weakened selection in humans that fails to remove deleterious mutations which result in diseases like dementia.
Valenzano also discusses their research on the microbiome of fish, mice, and humans, which includes a look at how the microbiome changes over time and during the ageing process, and how microbes interact with the immune system during the ageing process.
Tune in for the full conversation and visit https://www.age.mpg.de/science/research-laboratories/valenzano/ to learn more.
Professor Fábio Aguiar-Alves specializes in identifying bacteria common to staph infection. For example, he can identify the exact types of bacteria present on a patient before they face surgery in order to prevent serious bacterial infections. He tells listeners
Fábio Aguiar-Alves is an associate professor of Biochemistry and Cellular and Molecular Biology at Universidade Federal Fluminense in Brazil. While his initial studies focused on parasites, he became intrigued with bacteria during his PhD work and followed up with a postdoc at University of California, Berkeley, where he researched Staphyloccocus Aureus, a common staph infection.
He now works in molecular epidemiology, identifying bacteria in patients and looking for specific genes that relate to virulence and resistance. He can provide this information to help guide the doctors in specific treatments to prevent or treat bacterial infection. He explains what he's looking for after he does this DNA retraction. For example, if he finds a certain gene denoting resistance, he can tell the doctor not to use penicillin to treat this patient because it won't solve the problem. Ultimately, this serves to give the patient a specific antibiotic when needed rather than a broad spectrum antimicrobial agent.
He goes into more details about the process—specifically PCR (polymerase chain reaction) to identify the genes—which takes from 2 to 3 hours to figure out. Therefore, they can give a fast answer to the doctor about how to treat—much faster than past systems which delayed treatment considerably. He also explains the different methods for treating the resistant MRSA versus Staphyloccocus Aureus, how common each is in the general population, and how future advances include better mobility and even faster testing times. He also explains the role lateral gene transfer plays in the spread of MRSA.
Found out more by searching for his google scholar profile and listings. His papers are listed in NCBI under aguiar/alves and his University website is http://pesquisadores.uff.br/researcher/f%C3%A1bio-aguiar-alves.
Irina Higgins works to develop effective artificial intelligence models for Google's DeepMind project. She explains some essential tenants and goals, including
After finishing her PhD in neuroscience, Irian Higgins went into the tech world instead of academia and is part of Google's team that works at DeepMind, their artificial intelligence arm. She describes their work as a mix between academia and industry. Their mission is to build something that can solve any task at least as good as any human can. However, she explains that while there's a large group of researchers who think that we just need to put together single AIs who can perform one task and see what they can do in combination, she comments that such systems are still brittle—a little bit of noise can throw the whole algorithm off.
She adds that given how the complicated the natural world is, she doesn't think we can come up with enough narrow AIs to handle problems. At this point she brings in her neuroscience, trying to create a model able to make unsupervised transfers of learning as the brain does. For example, we as humans understand the abstract notion of a paddle and a ball and keeping the ball in the air and can transfer those ideas to another game. She adds that if we can get a computer to do that same transfer, that's a huge leap forward. She further describes some of the ways she's trying to get to that point.
To keep up to date in this field of research, she recommends following blogs in the discipline, such as Google's DeepMind blog: https://deepmind.com/blog, and finding AI research scientists on twitter.
Professor Paul Turner specializes in the evolution of viruses. He shares how researchers conceive of and approach viruses today, including
Paul Turner is the Rachel Carson Professor of Ecology and Evolutionary Biology at Yale University. In this conversation, he covers many key topics about viruses and virus RNA and how bacteria and viruses may coevolve. He explains that there are numerous ways bacteria have taken genes and functions from viruses and incorporated them into the bacteria to enable a new opportunity for bacterial life to continue. Further, our human genomes are full of what are recognizably virus genes, or "ghosts of infections past," and we're still not clear how these genes may function.
He also covers the tremendous potential for phages to fight infection as antibiotics lose their effectiveness. He talks about some of the roadblocks to this forward movement and how his lab is approaching this research as well as using viruses to better understand evolution as a process and examine pathogenic virus ecology.
Along the way he explains multiple current theories on viruses, virus RNA, and even touches on the exciting work in ocean genomics, a field that is able to look even closer at metagenomics. He also talks about the technology available, how now that scientists have more single-cell tools to study and examine viruses, he's more optimistic that we can access the individual cell level to see variation in how certain cells interact with "free riders" like viruses.
For more, see his page at Yale University, https://medicine.yale.edu/profile/paul_turner/, and the Turner Lab page, https://turnerlab.yale.edu/.
Clinician and researcher Lahari Rampur became interested in allergy studies when confronted with underserved populations in India followed by the amazing possibilities for treatments she found in her graduate work in New York. She's since spent her professional career pursing allergy and autoimmune disorder treatments. Dr. Rampur explains to listeners
Dr. Lahari Rampur is a clinical assistant professor in the Department of Medicine, Division of Allergy and Infectious Disease, at the University of Washington. The majority of her time is spent in clinical work involving allergy and autoimmune disorders. However, she also researches antibiotic allergies. She explains that while many people have a history of allergic reactions to penicillin and various antibiotics, alternatives can be more expensive and have bad side effects. Her research involves developing important protocols and guidelines therefore to identify who is truly allergic versus those patients who will be able to tolerate those antibiotics. In fact, she's found that 90% of those who've had reactions are able to tolerate the antibiotics at a later time.
She shares some general information about allergies with listeners, including genetics versus environmental factors and offers solutions to allergies, from dust mite control measures to allergy shots. She describes how allergy shots work to gradually teach the immune system not to over react to the introduced substance, affecting the behavior of cytokine cells. She also describes some exciting breakthroughs, including biologic medications that work well with certain types of asthma by blocking IgE antibodies.
For more, google her name and see her website at the University of Washington: https://aid.uw.edu/faculty/lahari-rampur-md
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