Mendelspod Podcast

In this episode, Theral delves into the groundbreaking role of microRNA as a cancer biomarker with Tim Williams, professor of clinical pathology at the University of Cambridge Veterinary School, and Paola Ulivi, a leading researcher at the Instituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori (IRST) in Italy. MicroRNA, which recently garnered its discoverers a Nobel Prize, has emerged as a powerful tool for detecting and tracking cancer progression.Williams and Ulivi share their latest research, highlighting how microRNA’s rise in cancer diagnostics parallels the evolution of fragmentomics, which analyzes cell-free and circulating tumor DNA. We explore the key differences between using RNA and DNA in biomarker development, the advancements in tools driving these discoveries, and the timeline for microRNA-based diagnostic tests to reach clinical practice.“There’s a lot of potential,” says Ulivi, “but the challenge in translating this into clinical practice will be the standardization and normalization of the process."Join us as we discuss the promise, obstacles, and future of microRNA in transforming how we diagnose and treat cancer. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.mendelspod.com/subscribe

Jacob Rubens is having quite a career.  Studying at  MIT in the Synthetic Biology Center with Professor Tim Lu, he invented gene circuits that allow engineered cells to do novel analog, digital, and hybrid computations, enabling the emerging field of “intelligent” cell therapies. In 2017, he was honored in Forbes 30 under 30 and, in 2021, in Business Insider’s list of 12 young serial entrepreneurs building the next generation of biotech. He has co-founded Kaleidoscope Biosciences, Sana Biotechnology, and the focus of today’s interview, Quotient Therapeutics.To understand what Quotient is up to, we must go back to basic biology and remember what are somatic genomics.  Germline mutations are changes to your DNA inherited from the egg and sperm cells during conception. Somatic mutations are changes to your DNA that happen after conception to cells other than the egg and sperm. These somatic mutations can lead to genetic conditions that affect your health. In truth, our bodies contain not one but trillions of divergent genomes, the sum of which we can call our “somatic genome.” Quotient Therapeutic studies this library of variant genomes that contains vastly more genetic information than we ever thought possible. In today’s show, Rubens says that the rise of somatic genomics offers a revolution in biology and that his company has a step up on those now getting excited about the field, including $100 million being invested by the NIH in this area of genomics.”This is some of the coolest science I have seen in my career,” says Rubens.   "The somatic genome is a revolutionary alternative view of what is going on in every cell.  All 30 trillion cells in our bodies have a distinct sequence of DNA. Two cells sitting next to each other may differ by thousands of base pairs.”Rubens says this new biology will lead to many new targets for drug discovery as well as biomarkers for diagnostics. How far has the company developed their platform—where are they at today?  Which disease areas are they pursuing for new drugs? Is the company itself pursuing drug development?  Join us as we explore somatic genomics in our series, “The New Biology.” This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.mendelspod.com/subscribe

Human genomics is complex. With new, scalable tools, we are unraveling that complexity. For example, we don’t just each have one genome; we have trillions, as each cell has a unique genome. Analyzing biology at the single-cell level continues to be one of the major frontiers in research.To learn how Single Cell Discoveries (SCD), a contract research organization in Utrecht, the Netherlands, has scaled and innovated in this field, Theral sits down with Mauro Muraro, cofounder and CEO of SCD. Muraro discusses the company's origins as a small university lab and its rapid growth due to increasing demand for single-cell and multiomic applications in biotech and pharma.The conversation delves into the transformative potential of single-cell technologies, addressing key topics like identifying rare cell types, single-cell atlases, and the challenges of handling the enormous data generated from these analyses. Muraro explains how Single Cell Discoveries is advancing the field with cutting-edge techniques, such as spatial transcriptomics and high-throughput sequencing, to push the boundaries of biological research and drug discovery.Why does a single cell require such a large sequencing capacity? What are the challenges in finding new higher-quality targets for pharma?  And how does SCD aim to push the boundaries of current single-cell technologies?One of the ways SCD helps pharmaceutical companies is by stratifying tissue by cell type to better find targets that will work. Muraro tells of a client working on neurodegenerative diseases who says, "It’s like doing a clinical trial in a dish." This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.mendelspod.com/subscribe

Vik Bajaj, co-founder of Verily and Grail, is now steering Xaira Therapeutics, where he's leveraging AI to revolutionize drug development. He discusses how machine learning can streamline the drug discovery process by simulating biological systems to predict interactions. Bajaj highlights the necessity of robust genomic datasets and the integration of AI with biotechnology for greater insights. He explores exciting AI applications, addressing challenges while envisioning breakthroughs that could reshape the industry.

Singular Genomics launched its fast and flexible mid-throughput sequencing platform, the G4, in the heady days of the pandemic when we saw a renaissance in new technologies and companies.At AGBT earlier this year, the company unveiled its latest offering in development, the G4X Spatial Sequencer, an upgrade to the G4 that unlocks the system to perform high-throughput in situ multiomics.  The platform will be capable of simultaneous direct RNA sequencing, targeted transcriptomics, proteomics, and fluorescent H&E from FFPE tissues at subcellular resolution. The G4X positions Singular to be the only company worldwide to offer capabilities for tissue-based in situ spatial multiomics and NGS on the same instrument.Singular's CEO, Drew Spaventa, joins us to discuss the G4X platform and the latest evolution in spatial biology.Drew says the field of spatial biology is a billion-dollar market, is growing rapidly, and the platform hits a sweet spot for throughput to bring down running costs. "The biggest issue people have right now in spatial is throughput cost per sample,” says Drew.  “It’s prohibitively expensive.”What early applications does the company see in their early service work?  When will the instrument be available?  And how does Drew see research evolving in the next couple years? This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.mendelspod.com/subscribe

Ellen Matloff, founder and CEO of MyGeneCounsel, is a strong advocate for the pivotal role of genetic counselors. She discusses the rapid transformation in genetic testing, with larger labs acquiring smaller ones, making genetic tests more mainstream yet raising concerns over quality counseling. Ellen emphasizes the changing responsibilities of genetic counselors, the importance of better compensation, and integration within healthcare. She also highlights the impact of precision medicine on genetic counseling and the need for improved accessibility in this evolving landscape.

Depending on your age, DNA sequencing is experiencing a second or third renaissance. New sequencing tools continue to make genomics one of the fastest-growing industries of all time. All this scaling can create a bottleneck in sample prep. Volta Labs, a company founded out of the MIT Media Lab by Udayan Umapathi, has just commercialized a new instrument for sample prep called Callisto. The instrument manipulates samples with electric, magnetic, and acoustic fields.   Udayan joins us today to describe the new instrument and comment on how sample prep is evolving today. Most importantly, the company wants to develop new apps with customized settings based on the customer's particular application, such as isolating really long, high-molecular-weight DNA for long-read sequencing. “The vision is to have a vast set of apps, similar to an iPhone.  We will continue to provide more and more apps that cater to various customers,” says Udayan in today’s show.What are the apps Udayan sees in the next few years?  And what is the ultimate sample prep in today’s world of sequencing? This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.mendelspod.com/subscribe

Genetic studies of human populations have become a major tool for drug development. In the last few years, these studies have moved toward comprehensive proteomics profiling as well. In late 2023, a paper was published in Nature by the Pharma Proteomics Project, which characterized the plasma proteomic profiles of 54,219 UK Biobank participants. This was a precompetitive biopharmaceutical consortium that sought to provide a mapping of 2,923 proteins that identified 14,287 primary genetic associations, of which 81 percent were previously undescribed.Chris Whelan was the lead author of this project paper, and he joins the show to discuss what’s next for these kinds of studies and their results. Whelan is a director of neuroscience on the data science and digital health team at Janssen Research & Development. He’s also chair and co-founder of the Pharma Proteomics Project. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.mendelspod.com/subscribe

This is a free preview of a paid episode. To hear more, visit www.mendelspod.comA new blood collection device offered by startup company Tasso is a blood lancet that collects whole liquid blood samples. Its ease of use for at-home collection could dramatically improve patient testing compliance and impact the scale of clinical trials.Ben Casavant is the co-founder and CEO of Tasso. He joins us to discuss the possibilities for at-home testing.  Ben and the company have raised over $100 million dollars.

Today, we continue “The New Biology” series with a non-reductive geneticist from Trinity College in Dublin.  Kevin Mitchell is the author of Free Agents: How Evolution Gave Us Free Will.The problem of free will has dogged philosophers and scientists as much as any question going back to the Greeks.  Determinism, typically argued by physicists, usually goes something like: the laws of physics predict the future, and therefore, there is no free will. In our lives, however, the experience of making choices is fundamental to our well being, to our culture and our system of morality.  There would not be a legal system without free will. Or is the Supreme Court just an illusion, as determinists say about free will?  Does the murderer always have an alibi? Kevin says at the core of the debate is the question of “the self" and whether it can be its own cause. Through several chapters, he develops the history of “motility” in life, the ability of single cells to move around.“The environment may be so inhospitable that you need to move, especially if you’ve been dividing and dividing and using up all the food. Being able to move is a really good trick, and then you must ask, well, where?  Which way should I move?  Moving toward a food source and away from a threat becomes selectable over time,” says Kevin.Does Kevin think of this single cell that has just learned to move as an "agent?”   (The Latin root for agent is “agere,” meaning to do, to move.) As life evolved, Kevin argues, it developed purpose and meaning which will guide it in a “top-down” way. What are the broad implications of Kevin’s work on free will for further study of biology and philosophy? How might his thinking extend to robots and AI?We finish with a discussion on reductive and non-reductive biology.Note: Coincidentally, another book written by a biologist arguing the other way on free will hit shelves at the same time Kevin’s book came out. In Determined: A Science of Life Without Free Will,  Stanford neuroscientist Robert Sapolsky uses biology to argue that we do not have free will. We have invited Robert to the program. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.mendelspod.com/subscribe