Mendelspod Podcast

Theral Timpson

Offering a front row seat to the Century of Biology, veteran podcast host Theral Timpson interviews the who's who in genomics and genomic medicine.

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Thursday · 4 min
Serge Saxonov on What’s Next for 10x Genomics
This is a free preview of a paid episode. To hear more, visit www.mendelspod.com 10x Genomics has been remarkably good at figuring out where biology is going next. In this wide-ranging conversation, co-founder and CEO Serge Saxonov explains why. Despite decades of genomics, “we still understand very little biology.” For 10x, the way forward has been to build better tools for measuring it and to work backward from the biological questions rather than forward from a particular technology. That philosophy helped drive the single-cell revolution and 10x’s move into spatial biology. Now the company has launched Atera, its new spatial platform designed to measure the whole transcriptome with single-cell sensitivity and at much greater scale. Customer shipments are expected to begin later this year. Saxonov argues that spatial is becoming something much bigger than another research niche. It’s a way of bringing molecules, cells and tissues into the same view. Going beyond RNA? Saxonov discusses 10x’s recent moves into proteomics and why he believes binder-based approaches currently offer the best path to scale. And he says 10x is investing directly in clinical diagnostics, pointing to therapy selection in oncology and autoimmune disease as two early opportunities. Getting closer to patients, he says, should also help 10x understand what its next generation of technologies needs to do. What would convince Saxonov that all this is succeeding? Not another instrument or another omic. It would be a measurable improvement in clinical-trial success. “The next decade is going to be wild,” he says.
August 20 · 5 min
“You Cannot Discover What You Cannot Make”: Lee Cronin on Programming Chemistry
This is a free preview of a paid episode. To hear more, visit www.mendelspod.com Those of us in biology tend to think that chemistry is rather straight forward. But today’s guest says there’s quite an art to synthesizing a molecule. A few years ago, Lee Cronin, a chemistry professor at the University of Glasgow joined Mendelspod for a sprawling conversation about the origin of life, alien biology, assembly theory, and his conviction that chemistry could become programmable. Now Cronin is back, and that last idea has become a company that now has a “chemifarm.” First let’s look at the problem. It is easy to assume that once a drug company has designed a promising molecule, the chemists more or less know how to make it. Not so. Chemistry remains surprisingly artisanal. A molecule that looks perfectly plausible on a computer may require too many steps to synthesize, depend on unstable intermediates, or require reactions that simply aren’t known. And chemists may not discover that until they’ve spent considerable time trying. This becomes an even bigger problem in the age of AI. Algorithms can propose vast numbers of new molecules, but which ones can actually be made? And if one can’t, is there another molecule nearby in chemical space that could perform the same function but be dramatically easier to synthesize? That’s the problem Chemify is trying to solve. “You cannot discover what you cannot make,” Cronin says in today’s interview. He spent 15 years developing χDL, a programming language that reduces the work of chemistry to a set of basic operations that machines can execute. Chemify’s software can then work backward from a desired molecule to determine a possible route for making it. Its robotic systems execute those instructions in the physical world, including chemistry requiring unusual temperatures and conditions. And its Chemifarms bring large numbers of these systems together so the process can be repeated at scale. The result is something Cronin calls a chemistry “hyperscaler.” A pharmaceutical company might bring Chemify a molecule proposed by its own AI system. Chemify can ask whether that molecule is realistically makeable, develop a route to it, physically attempt the synthesis, and feed what happened back into the system. If the molecule isn’t practical, the platform can suggest alternatives. Every success—and importantly, every failure—adds information about what parts of chemical space are actually accessible. Cronin’s ambition is enormous. He wants Chemify to become a sort of utility, the “AWS for all drug discovery companies.” Not another company competing to discover the next drug, but infrastructure that allows pharmaceutical and AI companies to turn digital ideas into physical matter.
August 18 · 47 min
All of Us Comes of Age. And So Does Its Funding: Josh Denny on the Next Phase of Precision Medicine
There are very few genomics projects with the level of ambition of the NIH All of Us Research Program. The latest release includes data from more than 747,000 participants, 535,000 whole genomes, 480,000 electronic health records, and—for the first time—long-read sequencing, proteomics, transcriptomics, and a large collection of information extracted from clinical notes. More than 24,000 researchers are now using the resource. But the program is also arriving at an important transition: roughly 80 percent of its original ten-year funding runs out this year. So what happens when a massive national research experiment begins to come of age? Josh Denny, CEO of All of Us, joins us to talk about what the program has accomplished, what researchers are beginning to learn from the data, and what comes next. We discuss the extraordinary scale and diversity of the resource and the growing use of genetics alongside electronic health records and other forms of health data. All of Us is beginning to move from building infrastructure toward producing discoveries that could affect patient care. Denny explains why the program’s diversity is not simply a matter of representation but a scientific necessity. The project has already identified roughly 1.3 billion genetic variants, including more than 275 million that had not previously been observed. That diversity becomes even more important, Denny argues, as medicine moves toward increasingly personalized predictions and treatments. “We are capturing such a richer population and so much more kinds of data that we can’t actually reason through it as humans,” he says. “If the data underneath it are highly biased and not representative, then we’re going to make the wrong conclusions.” We also discuss All of Us as a platform for a much broader picture of human health—from electronic health records and wearables to nutrition, the microbiome, multiomics, environmental exposures, and eventually pediatric data. Denny shares examples of participants whose lives have already been changed by medically actionable genetic results and describes how researchers can build new studies on top of the All of Us population. What is the next phase of the program and that of precision medicine? “We’re going to have to redefine our definition of disease,” Denny says. Rather than treating something like type 2 diabetes as a single condition, he imagines increasingly precise descriptions of an individual’s biology, exposures, risk, and response. After years spent building one of the largest health datasets in the world, All of Us is beginning to show what we might actually do with it. 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
August 13 · 41 min
Season Opener: Is Biology Having Its Newtonian Moment? with Rob Phillips, Caltech
Welcome to Mendelspod’s 16th season! It’s hard to believe we’ve been doing this for just over 15 years, following first and foremost the people reshaping biology and medicine. But also the technologies and ideas. Our original vision was to feature the “people behind the headlines” and you’ll see that what we continue to do in this first show of the new season. A sincere thank you to everyone who has listened, watched, subscribed, sponsored, recommended guests, shared a show, told your friends, and simply kept coming back. We have a terrific season ahead, with some of the biggest names in the life sciences as well as some you may not know yet who are asking entirely new questions. To begin, we wanted to go big picture. Rob Phillips, professor of biophysics, biology, and physics at Caltech and co-author of Physical Biology of the Cell, thinks this could be the “Newtonian moment” for biology. We have extraordinary amounts of data. What biology needs now, he argues, are concepts that can organize those observations into a more predictive understanding of life. “The data in biology is getting to the point where we have no excuse,” Rob says. The conversation ranges from the limits of molecular reductionism to the meaning of prediction, the role of AI, and why better measurement still matters enormously. Phillips makes the case for explanations at many different scales. Understanding a wildebeest migration through molecules, he says, would be like explaining the Golden Gate Bridge through its iron atoms. Rob is nothing if not provocative—in the best sense. His style is to pile up ideas and questions one on the other to propel his listeners into that creative space of wonder. “We need more opinions. We need more authenticity,” Phillips says. “I want to hear how people think about things differently.” 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
August 6 · 32 min
From the Archives: Erdinc Sezgin and the Physics of Living Cells
On Mendelspod, we’re always searching for scientists who are looking at biology in new ways. Sometimes that means a new technology. Sometimes it means asking entirely different questions. Erdinc Sezgin is bringing the tools of physics to biology. Sezgin is a group leader at the Max Planck Institute of Molecular Cell Biology and Genetics, where he heads the Membrane Biophysics Group. His research focuses on one of the most familiar yet least understood structures in biology: the cell membrane. In this conversation from April, Sezgin explains why the membrane isn’t a smooth sea of lipids, but a dynamic landscape of tiny molecular neighborhoods that constantly assemble, disappear, and reorganize. We discuss how he is using the tools of physics to better understand the membrane’s inner and outer lipid layers, each with distinct electrical properties. Sezgin also talks about his collaboration with Pixelgen Technologies, where Molecular Pixelation was used to study how changes in membrane charge reshape the cell surface. By knocking out a lipid-regulating complex, Sezgin and his colleagues showed that living cells can adopt surface features that alter immune recognition and may help explain how cancer cells evade destruction. It’s a reminder that major biological insights often arrive alongside new tools that make previously hidden phenomena measurable. Sezgin’s work is also a broader comment on scientific boundaries. Biology is not separate from physics or chemistry, but an expression of them in living systems. “Cells don’t have physics, chemistry, biology... It is life,” he says. 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
July 30 · 23 min
From the Archives: How Cellanome Is Changing the Way We Study Cell Function with Matthew Spitzer and Pier Federico Gherardini
One of the biggest technology shifts we saw in biology over the past year came from the young company, Cellanome. Instead of relying only on static single-cell snapshots, the Cellanome platform enables longitudinal observation of live cells. In this conversation, Pier Federico Gherardini, VP of Computational Biology at Cellanome, joins Matthew Spitzer of UCSF, whose lab is putting the Cellanome platform to work in cancer immunology. The new CellCage technology allows researchers to follow individual cells and their interactions over time, then pair that behavior with transcriptomic and other molecular readouts. As Gherardini explains, this creates “a new data type” that connects functional behavior directly to molecular biology. For Spitzer, the breakthrough is linking phenotype and function in the same individual cell. His lab can watch dendritic cells activate T cells, or T cells interact with tumor cells, and then ask what was molecularly different about the cells that actually performed the function. “Now we have measured the function of the cell and the phenotype for the same exact individual cell,” Spitzer says. The result is a new way to study cell biology that could have implications for cancer immunology, cell therapy, target discovery, and functional screening. 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
July 9 · 29 min
Agilent and Oxford Nanopore Discuss Bringing Long Reads to the Clinic with a Customer
Acute leukemia patients often wait days or even weeks for the full battery of molecular tests needed to guide treatment decisions. Dr. Parth Shah from Dartmouth believes long read sequencing can dramatically shorten that timeline. In this episode, Shah joins Agilent's Rita Shaknovich and Oxford Nanopore's Claire Attwooll to discuss some details of how long reads are beginning to move from research applications into routine clinical testing. Along the way, we explore the role of targeted enrichment, quality control, automation, and informatics in making these workflows practical for real-world laboratories. For Shah, the field has reached an inflection point. After more than a decade of development, he argues that long reads are finally positioned to make the leap into clinical genomics. “As we ask more complex questions of human biology, long read is probably going to be the best ammunition that we have,” he says. His team at Dartmouth has already demonstrated the potential in acute myeloid leukemia, where a long-read workflow can now generate a comprehensive molecular profile within 24 hours rather than the weeks often required by conventional testing. Shaknovich emphasizes that the opportunity is not simply generating more data, but generating better data. Long reads, she notes, can simultaneously capture mutations, structural variants, and epigenetic information, creating a richer biological picture than many existing approaches. Attwooll highlights the flexibility that has emerged in the long-read ecosystem. Researchers can now choose among whole-genome sequencing, targeted enrichment, and Oxford Nanopore’s adaptive sampling approaches depending on the clinical question. She argues that the field is moving from a niche technology toward a mainstream platform for translational and clinical applications. A recurring theme throughout the conversation is that no single technology will dominate every application. Whole-genome long reads, targeted enrichment, and adaptive approaches each have a role to play. As these methods move from research into routine testing, success will depend on more than sequencing alone. Agilent's established customer base, automation capabilities, quality-control tools, and experience supporting laboratories help provide the infrastructure needed to bring Oxford Nanopore's rapidly advancing long-read technology into practical clinical workflows. 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
June 30 · 4 min
Liquid Biopsy for the Tumor Microenvironment: with Vince Miller and Mirna Jarosz
This is a free preview of a paid episode. To hear more, visit www.mendelspod.com We’ve become remarkably good at reading cancer cells. Spatial biology enabled us to read them in context. Today we discuss a new Nature study suggesting that the tumor microenvironment—the immune cells, stromal cells, and surrounding biology that often determines whether a therapy succeeds or fails—can be measured from a simple blood draw, or liquid biopsy. To do that we’re joined by Dr. Vincent Miller, an oncologist and former founding Chief Medical Officer of Foundation Medicine, and Dr. Mirna Jarosz, CEO of LiquidCell Dx. The work introduces a striking idea. Rather than focusing only on mutations inside tumor cells, it identifies recurring spatial ecosystems within tumors and then shows that their signatures can be recovered from plasma cell-free DNA using methylation patterns. The implication is that liquid biopsy may soon reveal not only what mutations a tumor carries, but how its surrounding biology is organized before treatment ever begins. But wait. How can blood possibly contain information about spatial organization inside a tumor? That answer unfolds gradually on today’s show, making the final portion of the discussion particularly rewarding. As Jarosz explains, “We’ve condensed spatial biology to really critical and recurring biological programs. And then we can measure those in blood. So now we have that spatial insight of the tumor microenvironment in a liquid biopsy.” For Miller, the significance is ultimately clinical. “The tumor is almost like an organ,” he says. “The ability to understand how that organ is constructed and what structures are near one another and how they’re functioning... is really the underpinning” of why patients with seemingly similar cancers can have dramatically different responses to therapy. If this approach continues to hold up in larger clinical studies, liquid biopsy may expand from reading the genetics of cancer to reading its ecosystem. This shift could improve immunotherapy selection, longitudinal monitoring, and our understanding of cancer biology itself.
June 25 · 4 min
Can Liquid Biopsy Transform Chronic Disease? Hamed Amini and Soheil Damangir of Hepta
This is a free preview of a paid episode. To hear more, visit www.mendelspod.com For the past decade, liquid biopsy has largely been defined by oncology. Tumors shed DNA carrying mutations and epigenetic changes which allows researchers to detect cancer and monitor response. With this physicians are increasingly able to guide treatment. But chronic diseases are different. There is no tumor. Biological signals are subtle and quite d…
June 23 · 46 min
The UAE’s Big Bet on Genomic Medicine with Mohamed Alameri and Albarah El-Khani
The future of genomics has arrived in Abu Dhabi. On today’s show, Dr. Mohamed Alameri of the UAE Department of Health and Albarah El-Khani of M42 describe one of the most ambitious precision medicine efforts underway anywhere in the world: the Emirati Genome Program, which has already sequenced more than 900,000 genomes and is rapidly integrating that data into everyday healthcare. The UAE program is not only a large sequencing effort and database—soon to be made available for research anywhere—but a coordinated national strategy built on prevention, diagnosis, and long-term population health. Particularly striking is the UAE’s focus on inherited and autosomal recessive diseases, which occur at significantly higher prevalence in the region than in many Western populations. Rather than treating genomics as an isolated research exercise, the program has pushed aggressively into premarital screening, newborn genomic screening, pharmacogenomics, hereditary cancer risk assessment, and rare disease diagnosis. “We truly believe in the philosophy of ‘sequence once, analyze for life,’” says El-Khani. “Imagine a society where every individual from birth holds a whole genome sequence throughout their life. How powerful is that tool at every intersection of public health, clinical care, and screening?” The scale of the project is already yielding discoveries difficult to achieve elsewhere. According to Alameri, roughly 12% of the variants identified in the Emirati population are not represented in existing global databases, underscoring just how underrepresented Middle Eastern populations remain in genomics research. In some cases, variants previously considered pathogenic in European populations appear to behave differently in Emirati patients, opening entirely new biological questions. Perhaps the most impressive aspect of the program is the degree to which genomics has been operationalized across the healthcare system. The UAE has invested heavily in physician education and public engagement to move genomics from bench to bedside. Our guests describe a healthcare ecosystem where genomic reports, pharmacogenomic guidance, and hereditary risk assessments are increasingly available directly within clinical workflows. “The vision was not sequencing everyone for its own sake,” says Dr. Alameri. “It was to build a national asset that could support more predictive, preventative, personalized healthcare for our population and for future generations.” There is always hype in genomics, as with other emerging technologies. But the UAE effort is already very comprehensive and clinically grounded. This is genomics functioning as healthcare infrastructure in real time. 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
June 18 · 41 min
Ryan Flynn of Harvard on Non-Coding RNA
On today’s show, Dr. Ryan Flynn of Harvard Medical School and Boston Children’s Hospital takes us into a newly emerging layer of biology: the architecture of the cell surface itself. Flynn first gained attention for the discovery of glycoRNA — RNA molecules displayed on the outside of cells — a finding that challenged the traditional picture of the cell surface as a world composed primarily of proteins and glycans. RNA has long been understood mainly as a carrier of genetic information (messenger RNA), but Flynn’s work has show that it has other functions critical to basic processes in the cell. As we’ve been hearing on the program, biology has largely been a science of inventory. Throughout today’s conversation, Flynn argues that molecular organization itself may be a fundamental biological variable. Not simply whether a molecule exists, but where it exists, what it is adjacent to. Using technologies such as Pixelgen’s Proximity Network Assay, his lab is beginning to map the “cell surface architecture,” or the arrangement of proteins, glycans, and nucleic acids that together govern signaling and cellular behavior. The implications stretch across biology. Flynn describes early evidence that extracellular RNA can tune classical signaling pathways such as VEGF-mediated angiogenesis by physically modulating how growth factors engage receptors on endothelial cells. Remove the RNA, and growth factor binding changes dramatically. Rather than acting as a simple on/off switch, the RNA appears to function as a finely tuned regulatory layer controlling signaling strength. In cancer, where cell-surface signaling drives growth, invasion, and immune escape, looking at the organization of the cell surface may determine whether therapies can physically access their targets. Flynn points to bispecific antibodies and T-cell engagers as examples of drugs whose function already depends on proximity and molecular arrangement, even if work in biology has not fully measured those variables before. 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
June 11 · 32 min
Gary Schroth on Connecting Cellular Behavior to the Transcriptome
For decades, biology has been driven by the powerful notion that if we could sequence enough genomes, transcriptomes, epigenomes, then we could finally explain the cell. On today’s show, Gary Schroth, the Chief Scientific Officer at Cellanome, argues that something essential was still missing. Schroth spent nearly two decades at Illumina helping build the sequencing revolution. He has now joined Cellanome to pursue an expanded vision of biology that connects transcriptomics with live-cell imaging. Our conversation centers around two newly released preprints describing the company’s platform and its application to CRISPR screening, where imaging and transcriptomic data are explicitly linked in the very same cells. “What we show in a few examples in both papers,” Schroth explains, “is that it’s the combination of transcriptome information and imaging information that really gives us the complete story of what that cell is doing.” That idea—linking what researchers literally see under the microscope with the molecular state of the exact same cell—emerges as the core concept of the interview. Rather than treating imaging and transcriptomics as separate measurements, Cellanome brings them together in a longitudinal workflow where cells can be observed alive over time and then profiled at the transcriptomic level. “Sequencing has certainly taught us a lot about cells and sort of the parts list inside cells,” he says. “But it doesn’t really explain biology.” Will this be the next phase of post-genomic biology where the field moves beyond static snapshots toward directly observing cellular function as it unfolds? 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
June 9 · 27 min
Two-Thirds of High-Risk Breast Cancer Patients May Avoid Chemotherapy According to Veracyte Data Presented at ASCO
Today on the show, we’re discussing a new study just presented at ASCO 2026 that could change how chemotherapy decisions are made for a large group of breast cancer patients. During ASCO we spoke with Phil Febbo, Chief Scientific and Medical Officer at Veracyte, and John Leite, the company’s Chief Commercial Officer, looking at the results from the OPTIMA study, a large prospective trial involving roughly 4,500 patients with clinically high-risk ER-positive, HER2-negative breast cancer. The study found that about two-thirds of these patients could safely avoid chemotherapy when treatment decisions were guided by the Prosigna test. “What the Optima study shows definitively is that those women with low Prosigna score do not benefit from chemotherapy,” Febbo explains. “They get all the side effects… without any benefit.” The data generated favorable attention at ASCO. The study produced prospective level 1A evidence, the highest standard for predictive testing, and addressed one of the central problems in breast cancer care: determining which patients actually benefit from chemotherapy and which patients may be exposed to toxic treatment unnecessarily. Our show also looks at the broader evolution of molecular diagnostics in oncology. Prosigna runs on whole transcriptome sequencing, creating opportunities not only for current clinical decision-making, but also for future translational research into tumor biology and treatment response. “We need the full complement of the transcriptome to understand what is the faulty circuitry and how do we shut it off therapeutically,” Leite says. Veracyte has moved quickly from clinical validation to rollout. The company already has the assay prepared for U.S. launch immediately following the ASCO presentation. If only it worked out this way every time. It’s the kind of direct through-line between biology, clinical evidence, and improvement of human life that molecular diagnostics companies strive for each year. Note: For more in-depth discussion on the OPTIMA study and the launch of Prosigna, sign up for an upcoming webinar at GenomeWeb here. 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
May 29 · 31 min
Building the Diagnostic Layer of Modern Cancer Care with Rita Shaknovich and Karina Kulangara of Agilent
For years, precision oncology has largely been discussed through the lens of breakthrough drugs. But there’s another story running underneath modern cancer care: the quiet rise of companion diagnostics. These tests are increasingly deciding who receives those therapies in the first place. In many cases, the real bottleneck is no longer discovering a drug target. It’s building a reliable system for identifying the right patient at the right moment in the disease. That challenge sits at the center of this conversation with Rita Shaknovich, Chief Medical Officer for Life Sciences and Diagnostis, and Karina Kulangara, Associate Vice President of R&D in Companion Diagnostics at Agilent Technologies. Agilent has always had a major role in this field. Rita and Karina explain how companion diagnostics evolved from the original Herceptin test into a vision for a much broader ecosystem spanning pathology, automation, regulation, and global clinical deployment. We dive into Agilent’s recent FDA approval expanding PD-L1 IHC 22C3 PharmDx into ovarian cancer, a development both guests describe as particularly meaningful given the historically poor outcomes associated with the disease. As Rita puts it: “Precision medicine is based fundamentally on scientific truth . . . it brought real results for patients. It brings better survival for patients, fewer side effects from the medication.” Karina offers one of the clearest explanations we’ve heard for why immunohistochemistry or IHC has endured so long in modern oncology. “It’s the ability to detect protein biomarker in the spatial context of the tissue,” she explains, emphasizing that location and cellular context can fundamentally shape how therapies work. What emerges is a picture of precision oncology that is becoming less exotic and more routine. We’re talking not just new drugs, but an entire clinical and technological infrastructure which is designed to match therapies to biology more effectively and over time. 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
May 28 · 44 min
Mapping the Multi-Omic Era with Eric Green of Illumina
Dr. Eric Green returns to Mendelspod in a new role: Chief Medical Officer of Illumina. After more than three decades at the National Human Genome Research Institute, where he helped guide genomics from research initiatives to clinical reality, he now joins one of the industry’s most influential companies at a moment when the field is expanding beyond DNA alone. Green takes us on a tour around the world of multi-omics, which he says is not a branding exercise but a practical response to the limits of sequence data by itself. Genomics remains foundational, but many clinical questions require additional layers of biology, including RNA, epigenomics, proteomics, and single-cell analysis. As he puts it, “DNA sequence alone may not reveal it.” The discussion highlights rare disease as one of the clearest examples. Genome sequencing can solve roughly half of suspected cases, Green notes, but many patients remain undiagnosed because the relevant signal may lie in RNA splicing, epigenetic regulation, structural variation, or downstream protein effects. In those settings, multi-omic approaches can provide the missing evidence needed to move from uncertainty to diagnosis. In oncology, the challenge is different. Cancer genomes can be highly complex and heterogeneous, making it difficult to distinguish driver events from background noise. That is one reason why researchers and clinicians are increasingly incorporating methylation markers, transcriptomic data, and proteomic signals into early detection, disease sub typing, and monitoring strategies. Green also emphasizes that the next bottleneck may be less about generating data than interpreting it. “The human brain is not going to be the thing that’s going to crack this nut,” he says. “It’s going to be AI and computational biology.” The result is an overall picture of where the field may be headed as we go from genomic medicine to a broader molecular medicine with multiple data types that will improve diagnosis, stratify disease, and guide care worldwide. 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
May 21 · 4 min
Inside Proteomics at Thermo Fisher with Yan Zhang
This is a free preview of a paid episode. To hear more, visit www.mendelspod.com For years, proteomics was described as the missing layer of biology. Why missing? Because measuring proteins at scale turned out to be vastly harder than sequencing DNA. That may finally be changing. In today’s episode Theral speaks with Dr. Yan Zhang, President of Proteomic Sciences at Thermo Fisher Scientific, about the rapid evolution of large-scale p…
May 19 · 23 min
Separating Epigenetic Signals Improves Early Cancer Detection with Rob Osborne, Biomodal
We’ve gotten very good at reading DNA. We’re just beginning to understand how to read its state. On today’s show, Rob Osborne, Senior Vice President of R&D at Biomodal, discusses new evidence that separating two epigenetic marks—5-methylcytosine and 5-hydroxymethylcytosine—can improve early cancer detection from liquid biopsy. In a recent Nature Communications Medicine study, his team showed that analyzing these signals independently in circulating DNA significantly enhanced detection of Stage I colorectal cancer compared with approaches that combine them. The advance does not require new sequencing hardware. Biomodal’s approach uses a sample preparation kit compatible with existing platforms, paired with bioinformatics tools, potentially lowering the barrier to adoption while expanding the information content of standard sequencing workflows. The underlying insight is biological as much as technical. Most methylation assays collapse 5mC and 5hmC into a single signal, masking early transitions in gene regulation. Osborne describes this as “squishing them into one output,” a simplification that can obscure meaningful changes in disease onset and progression. By separating the signals, the study identified patterns that emerge earlier in tumor development, offering a more sensitive window into disease biology. But the deeper message of the interview is that this work may only scratch the surface. “I think that we’re just at the beginnings of really understanding this biology,” Osborne says. 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
May 15 · 4 min
Digital Controls for Cancer Drug Trials? Irina Babina, Concr
This is a free preview of a paid episode. To hear more, visit www.mendelspod.com On today’s show, a fascinating discussion about digital twins for medical research— leading to the 64 million dollar question of how much of the current AI wave in healthcare may eventually prove real. Drawing on her background in cancer research and now as CEO of Concr, Dr. Irina Babina joins us to argue that the future of oncology may depend less on g…
May 7 · 37 min
Solexa Co-Inventor Shankar Balasubramanian on Six-Base Sequencing and What's Next in Genomics
An inventor of Solexa sequencing by synthesis has a new idea. On today’s show, Sir Shankar Balasubramanian revisits the accidental origins of Solexa sequencing, born not from a sequencing project at all, but from curiosity-driven experiments watching DNA polymerase at work. What followed helped transform DNA sequencing from a specialized pursuit into a routine engine of modern biology. But as Shankar makes clear, the biggest surprise may not have been genomics itself—it was how next-generation sequencing became a universal readout for biology, powering everything from single-cell and spatial biology to entirely new ways of probing molecules and mechanisms. Our conversation then turns to his latest venture, Biomodal, and the emerging world of 6-base sequencing. Shankar explains why distinguishing 5mC and 5hmC matters, and how six-base sequencing may improve early cancer detection. 6-base sequencing could also aid researchers in the exciting frontier of neurobiology. As always with great scientists, the story widens beyond any single technology. Shankar closes by reminding us that discovery follows better measurement. As our tools improve, biology will continue to surprise us. “That is what research is. It’s stepping into the unknown,” he says. 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
April 30 · 32 min
The Next Frontier in Biology: Physics? Erdinc Sezgin of the Karolinska Institute
There’s a famous line attributed to Ernest Rutherford, the father of nuclear physics: “All science is either physics or stamp collecting.” It’s still provocative. But it’s unfair to biology. Long before today’s omics era, biologists were uncovering causality everywhere from evolution and natural selection to Mendelian inheritance. They have never merely catalogued life. They have explained it. But modern biology has also generated extraordinary inventories of genes, proteins, and pathways, and those inventories now invite a deeper systems-level question: how do the parts behave together in living cells? Could new precise physical measurements aid biology and medicine? Todays’ guest, Erdinc Sezgin, is an Associate Professor at Karolinska Institute and recipient of the Biophysical Society Early Independent Career Award. His lab is bringing physics to biology. For example, Sezgin studies the cell membrane not as a passive wrapper, but as an active, dynamic system whose physical properties of fluidity, viscosity, charge, and organization help determine how cells signal and survive. His hope is to improve ways to measure these biophysical properties. Sezgin discusses his recent collaboration with Pixelgen Technologies, where Molecular Pixelation was used to study how changing membrane charge reshapes the cell surface. By knocking out a lipid-regulating complex, Sezgin and his colleagues showed that living cells can adopt surface features that alter immune recognition and may help explain how cancer cells evade destruction. It’s a reminder that major biological insights often arrive hand-in-hand with new tools that make previously hidden phenomena measurable. The conversation closes on a broader point about scientific boundaries. Biology is not separate from physics or chemistry, but an expression of them in living systems. “Cells don’t have physics, chemistry, biology. . . It is life,” he says. 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

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