Finding Genius Podcast

Most listeners are familiar with circadian rhythms, but Professor Zhu is working on less-studied 12-hour cycles and how they affect our well-being. He talks about his research, explaining How 12-hour rhythms match the tidal shifts and patterns, Why this 12-hour rhythm probably evolved before the circadian rhythms, and How a better understanding of the physiologies of ultradian rhythms might lead to Alzheimer's and other disease treatments. Bokai Zhu is an assistant professor in the Department of Medicine in the Division of Endocrinology and Metabolism and the Aging Institute at the University of Pittsburgh. He's working on biological rhythms, also known as oscillations, and specifically narrowed his study to research ultradian rhythms, which signifies 12-hour cycles, rather than the more commonly-studied circadian rhythms. Thus far he's found evidence that 12-hour rhythms originated to adapt to the 12-hour tidal rhythms, which we see in crustaceans. Furthermore, Zhu believes as we've evolved from the sea, humans and other animals have kept this 12-hour rhythm. In other words, this same tidal pattern followed by our evolutionary ancient ancestors is ingrained in our body clock. He discusses how he is conducting studies in mice to better understand this cycle and how it might regulate our systems. He makes an interesting analogy to morning and evening rush hour, how these 12-hour switches of increased activity present more risk for bodily damage like misfolded proteins. He's also found potential connections to memory issues because the hippocampus is especially engaged in the 12-hour cycle. Listen to learn about these issues and more. For more information, see his web site at the university and search for recent news articles covering his research: www.isb.pitt.edu/people/faculty/bokai-zhu-phd Available on Apple Podcasts: apple.co/2Os0myK

Professor Girguis studies microorganism in the ocean and their contributions that make our planet habitable. In this conversation, he explores How and why some microbes live in these extreme environments around hydrothermal vents and methane seeps; How these chemo autotrophs, or organisms that feed off of chemicals, connect to life in the upper reaches of the ocean and what that means to fisheries; and Why a reframing of ocean science is important in understanding and taking care of the interconnectedness of our biosphere. Peter R. Girguis is a professor of Organismic and Evolutionary Biology at Harvard University. He works in a field of molecular biology that studies microbes and animals that live in the ocean, especially microbial organisms that interact with metals like iron and magnesium, which he describes as akin to the multivitamins of the ocean. His microbiology study focuses especially on bacteria and archaea. These microbes inhabit environments, like hydrothermal vents and methane seeps, to feed off the released metals, which are toxic to most animals. Professor Girguis utilizes molecular biology to understand how these microbes play a role in moving energy from the abiotic world, or nonliving structures like rocks, to the biotic world. Significantly, this microbiology study connects to the food chain. He mentions one study that shows how plankton feed on these microbes which in turn feed small fish that are eaten by the larger fish off the coast of Chile, which are integral to the fishing industry there. He describes other elements to this underwater architecture, from methane ice to giant sulfide structures, and how some fish use these extreme environments to rid themselves of parasites. He also posits a new view of ocean science that is much more outward looking and should engage people from all over the world. To find our more, see his lab's website: girguislab.oeb.harvard.edu. Available on Apple Podcasts: apple.co/2Os0myK

Karl Hassan researches antimicrobial resistance specific to hospital-associated pathogens. He talks about his work towards developing compounds that can overcome this resistance. He explains The two main types of resistance, acquired and intrinsic; Which pathogens are the toughest to combat, namely gram-negative bacteria; and How understanding a specific gene expression for a bacteria may provide answers toward generating compounds to kill that bacteria. Karl Hassan is an ARC Future Fellow at the School of Environmental and Life Sciences at the University of Newcastle in Australia. He studies antimicrobial resistance of pathogens common to hospital settings. He explains that these pathogens adapted to the hospital niche and have become superbugs. Because big pharmaceutical companies experience low profits from antibiotic development, the research has been taken up by university scholars like Hassan. He talks more about the inner workings of the bacteria, especially the gram-negative bacteria, which present more of a challenge because they have two membranes and are intrinsically resistant. He explains more about the mechanics and cell architecture and then shares an exciting find: they were able to identify a gene that was unknown and verified that when expressed, it offered resistance to the bacteria. They believe, based on tests, it may code for the efflux pump protein. Understanding how different families of efflux pumps work will help develop compounds that can infiltrate the bacteria cells. He finishes by explaining the process for how something like this find can lead to eventual compound production. For more, see his page at the University of Newcastle: www.newcastle.edu.au/profile/karl-hassan#career Available on Apple Podcasts: apple.co/2Os0myK

Jen-Tsan Ashley Chi: I was born and grew up in Taiwan. I obtained my MD from National Taiwan University and PhD from Stanford University. From my post-doctoral training with Dr. Patrick Brown at Stanford, I have been using genomic analysis and gene expression to dissect the influences of various tumor microenvironmental stresses in human cancer and tumor heterogeneity. Since arriving at Duke University, we discovered the presence of abundant and diverse species of RNAs in mature erythrocyte, a cell type long thought to lack any DNA or RNA. Since then we have pioneered the efforts to apply the genomic analysis of erythrocyte microRNAs to dissect the phenotypic variations among sickle cell diseases and blood storage. From the investigation of erythrocytes, we have been interested in the role of erythrocyte RNA in the malaria parasites, including the recent adoption of single cell RNA-Seq technology of malaria parasite pioneered by Dr. Katie Walzer during her thesis work in my lab. Katelyn Walzer: For over ten years, Dr. Katelyn Walzer has studied the genetics and genomics of multiple apicomplexan parasites, including Toxoplasma gondii, Plasmodium falciparum, and now Cryptosporidium parvum. She completed her PhD in 2018 under the guidance of Dr. Jen-Tsan Ashley Chi at Duke University, where she studied the malaria-causing parasite P. falciparum using high-throughput genomic technologies, including single-cell RNA sequencing. Her work, published in multiple journals including mSphere and PLoS Genetics, identified distinct gene expression differences between male and female parasites during the transmissible sexual stage and uncovered unexpected transcription of genes during multiple times in the P. falciparum life cycle. These findings imply that significant transcriptional diversity allows the P. falciparum parasite to survive its dynamic host environment. Now a post-doctoral fellow in Dr. Boris Striepen's lab at the University of Pennsylvania, Dr. Walzer studies the transcriptional regulators of the C. parvum life cycle and has used single-cell RNA sequencing to determine the genes expressed during the asexual and sexual stages. Further work will focus on functionally characterizing stage-specific regulators and determining single-cell gene expression of the host immune response. Walzer KA, Fradin H, Emerson LY, Corcoran DL, Chi JT (2019) Latent transcriptional variations of individual Plasmodium falciparum uncovered by single-cell RNA-seq and fluorescence imaging. PLOS Genetics 15(12): e1008506. https://doi.org/10.1371/journal.pgen.1008506 Walzer KA, Kubicki DM, Tang X, Chi JT. Single-Cell Analysis Reveals Distinct Gene Expression and Heterogeneity in Male and Female Plasmodium falciparum Gametocytes. mSphere. 2018;3(2):e00130-18. Published 2018 Apr 11. doi:10.1128/mSphere.00130-18 Researcher Katelyn Walzer and her Ph.D. mentor Dr. Jen-Tsan Ashley Chi used single-cell analysis to study the malaria-causing parasite, Plasmodium. Dr. Walzer is now studying another parasite called Cryptosporidium. In this podcast, they discuss How Cryptosporidium infects hosts and the dangers it poses, especially for children, Past bulk-sequencing techniques for parasites and what they missed in analysis, The mechanics for single-cell genomics analysis, what it offers microbiology, and advantages specific to fighting Cryptosporidium. Jen-Tsan Ashley Chi, MD, PhD, is an associate professor at the Center for Genomic and Computational Biology at Duke University School of Medicine. His former microbiology student, Katelyn Ann Walzer, PhD, is currently working on her post-doc at the University of Pennsylvania with single-cell analysis. They tell listeners about their specific findings on Plasmodium and Dr. Walzer's current focus on Cryptosporidium, a parasite that causes a diarrheal disease, and what else she hopes to study regarding the parasite. She gives some background on the parasite, describing how detrimental it can be for children in some countries of Africa who've already suffered from other diseases. Cryptosporidium can actually reactivate and cause chronic infection in these children, affecting their general health and quality of life. Dr. Walzer explains how single-cell genomics analysis has allowed her to identify which genes are expressed in the two different matting types (sexual and asexual). Dr. Chi explains how this technique also helped in Plasmodium research because mating is the only way to achieve intrapersonal human transmission, and identifying males and understanding the stages of development in both parasites may offer ways to block their development. Dr. Walzer explains additional findings, plans for upcoming research, and her goals to discover information that will help develop better treatments for infection by Cryptosporidium. For more information, search these researchers in Google Scholar. Available on Apple Podcasts: apple.co/2Os0myK

Assistant Professor at Icahn School of Medicine at Mount Sinai, Dr. Augusto Rodriguez, talks about the scope of his work and research on different aspects of liver oncology. In this episode, you will learn: Which underlying diseases are the main causes of liver cancer, and how long it generally takes for liver cancer to develop How many therapies have been approved for use in patients with liver cancer, and why it has been challenging to determine which type of therapy will work best for a particular patient What it means for a liver tumor to be heterogenous and why it's significant Dr. Rodriguez's work centers around the goal of incorporating molecular information from tumors into tools that can be applied in the clinical setting to improve prognosis predictions, and developing novel methods for early detection of liver cancer. The current gold standard for early detection of liver cancer is a combination of abdominal ultrasonography to look for evidence of small tumor formation, and blood tests to identify the levels of a certain protein known to be elevated in patients with liver cancer. So, what's wrong with the current gold standard? Dr. Rodriguez explains that in addition to operator error with regard to the ultrasound procedure, it requires patients to travel to an imaging center every six months, which is difficult to manage for many people. Due to the inconvenience and difficulty presented by compliance with the gold standard protocol, many people end up developing liver cancer that goes undetected for far too long. A potential solution that Dr. Rodriguez has his eyes on is a technology called liquid biopsy. In essence, it entails an analysis of tumor components within the bloodstream, such as fragments of DNA from tumors or extracellular vesicles released from tumors. The detection of such components in a blood sample taken at the point of care can detect liver tumors when they are very small, leading to better overall prognosis. In addition, liquid biopsy may address another complication in the area of liver cancer treatment, which is the determination of how best to sequence the many therapies that have become available in recent years. Dr. Rodriguez discusses a number of fascinating topics. Tune in for all the details. Available on Apple Podcasts: apple.co/2Os0myK

Dr. Ray Kaplan is a professor in the Department of Infectious Diseases at University of Georgia. He joins the show to discuss the details of his research on parasitism and drug-resistant parasites. Tune in to discover: How a dog contracts heartworm disease and how the disease progresses How a hookworm infection in a dog progresses differently than it does in a human, and what type of research is being done in Kaplan's lab to study drug-resistance in hookworms in dogs Why it has been difficult to tackle the problem of drug resistance in parasites, and where the research currently stands Dr. Kaplan's interest in parasites was sparked after he found himself working in a parasitology lab as an undergraduate at Virginia Tech. He continued conducting research on parasitology while in veterinary school, and eventually entered academia to become a professor and focus more exclusively on his research. He studies primarily parasites of livestock and dogs, and aims to better understand and solve the problems posed by increasing numbers of drug-resistant parasites. Dr. Kaplan discusses the life cycle of common parasites in dogs, what happens when a human being is infected by hookworms, the coevolution of the gut microbiome and intestinal worms, evidence which suggests that some parasites may be critical to the human immune response and protection against autoimmune diseases, what mechanisms are used by parasites that enable them to complete their life cycles, challenges and roadblocks to progress in parasitology, drug resistance of roundworms infecting turkeys, and so much more. For information on these and related topics, check out the following: https://vet.uga.edu/person/ray_m-_kaplan/ https://www.wormx.info/ Available on Apple Podcasts: apple.co/2Os0myK

Professor Robert Poulin's interests center around how and in what ways parasites manipulate the behavior of their hosts. He joins the show to discuss his fascinating research. In this episode, you will learn: Why a parasite would benefit from making its host insect take on the appearance of a bright red berry How an examination of the brain cells of infected insects could shed light on the pathways by which host behaviors change How a parasite's microbiome and the genomes of the microbes within it could help explain the mechanisms underlying parasite-driven behavioral modification of hosts Over the course of millions of years, parasitism has been gradually shaped and enhanced by evolution, resulting in parasites that have the amazing ability to induce behavioral and physical modifications in their hosts in ways that ultimately benefit the parasite. Consider, for instance, the hairworm, which is a parasite that grows inside a terrestrial insect in coil-like fashion until it becomes two to three feet in length, at which point it induces the insect to essentially commit suicide for its survival; the hairworm causes the insect to search for and jump into a body of water, where the hairworm can then emerge from the parasite (killing it in the process), find a mate, and reproduce. This is just one example of a parasitic relationship that Poulin hopes to better understand. In part, his research involves an examination of gene expression within the genome of the brain cells of infected host insects. Poulin is also interested in other mechanisms by which parasites manipulate hosts, such as those that may involve the microbes that parasites carry with them, or the presence of symbiotic viruses that manipulate host behavior. Among other topics, Poulin discusses how parasites are so effective at evading host immune systems, counter-adaptations to host defenses, examples of how parasites can form part of a larger ecosystem, which tissues are preferential for parasites to reside in and why, and so much more. Tune in for all the details and learn more about Poulin's research by visiting https://www.otago.ac.nz/parasitegroup/home.html. Available on Apple Podcasts: apple.co/2Os0myK

Ponni Perumalswami treats patients who have advanced liver diseases. She also is working to reach communities at risk for viral hepatitis B and C to connect them to testing, education, and healthcare. She explains The differences, such as transmission means, between hepatitis B and C; The reason why some foreign-born communities are at risk and how her group is trying to make their way into the center of these groups; and Why these diseases of the liver, while usually asymptomatic for years, can cause damage leading to treatments like liver transplantation. Ponni Perumalswami is an associate professor of medicine in the Division of Liver Diseases at Mt. Sinai School of Medicine. She tells listeners that there's an at-risk population for hepatitis B and C that she and her colleagues are targeting. In the U.S., while the diseases are less common in the general population, at-risk groups who immigrate from areas with higher rates, specifically Asian and African-born communities, are hard to reach. Because they may not have insurance and are not English speakers, they aren't in touch with primary care doctors who might normally screen for these diseases and they can be asymptomatic for years. Her outreach efforts include testing within the communities and awareness-raising efforts. Dr. Perumalswami explains how these diseases work. She explains that hepatitis B is a DNA virus that largely infects foreign-born populations because the U.S. has had the means to vaccinate and test for this disease. It spreads by a vertical transmission from mother to child. Hepatitis C is transmitted through blood exposures, so through intravenous drug use, blood transfusions, and organ donations done before 1992 when testing became available. Even though each can exist in the body silently for years, they can still do tremendous damage in the liver, and increase one's risk for cirrhosis, cancer, and other disease of the liver that may need liver transplantation. For more, see the Mt. Sinai Liver Diseases Division website https://www.mountsinai.org/care/liver-diseases/research Available on Apple Podcasts: apple.co/2Os0myK

Professor Nicolas Vabret has had an almost lifelong interest in viruses, and has been studying them since obtaining his PhD in 2011. He joins the show to discuss a number of interesting topics, including the following: How the two main arms of the immune system differ in function, and the nature of immune cells vs non-immune cells How an examination of the cytokines produced in response to the COVID-19 virus might shed light on why and whether some patients will develop a very serious form of the illness and some will remain asymptomatic What approaches have been and are currently being taken to find a treatment for HIV What happens as soon as a virus enters the body? What allows the body to recognize non-self cells and to respond accordingly? Some cells have the ability to detect the presence of viruses and bacteria that enter the body, and activate the first step in the innate immune response, which eventually leads to the activation of the second phase of the immune response. Vabret is particularly interested in understanding the early molecular mechanisms that make this possible. He describes the differences between the innate immune response and adaptive immune response, the role and function of pattern recognition receptors, RNA production, the importance of cytokines in the response to virally-infected hosts—in particular those infected with COVID-19, viral strategies for counteracting immune responses, characteristics of the HIV virus and chimpanzee versus human immune responses to it, current research in the field of immunology, and so much more. Available on Apple Podcasts: apple.co/2Os0myK

Vivek Mutalik is a synthetic biologist who studies biochemical energy and uses tools to understand how bacteria survive in their environment. He's currently focused on bacteriophages. He discusses Investigating how bacteria survive phages including bacterial defenses, How phages subvert these bacterial defenses in turn, creating an arms race, and Applications these studies can be used for, from therapeutic treatments like phage therapy to diagnostic tools to industrial eradications of biofilms. Vivek Mutalik is a research scientist at Lawrence Berkeley National Laboratory in the Environmental Genomics and Systems Biology Division as well as the Biological Systems and Engineering Division. He works with two key questions: how do phages and bacteria interact and how can scientists engineer phages. The goals connecting these foundational and engineering aspects include using phages for microbiome work and for eliminating pathogens. He explains his work studying the genes and mechanistics of bacteriophages by first giving an overview of the vast diversity and huge number of phages. He remarks that scientists know that they are virtually everywhere on earth, yet hardly know anything about their impact. He explains that there are different types of phages, some that infect specific bacteria and some that are broad spectrum, able to target lots of different bacteria. He says that while we don't understand how this specificity happens and what their design rule is—the key of phage biology—his research hopes to change this and better understand the engineering of these phages. His research studies the phages' genes to understand which genes encode which function. He explains some techniques and findings in more detail and says we need to understand this foundation to manipulate the microbiome so practitioners can get rid of specific microbes, not healthy ones, with precision. To find out more, find him on twitter as @vivek_mutalik and see his lab web site: biosciences.lbl.gov/profiles/vivek-mutalik/ Available on Apple Podcasts: apple.co/2Os0myK