Advertise on podcast: The Pauling Principle

Designing functional RNA for therapeutics is notoriously hard, but gRNAde changes the game. This geometric deep learning model generates high quality RNA sequences from target 3D structures. It outperforms Rosetta, slashes design time to seconds, and hits 50% success in wet-lab tests on complex folds. Chaitanya Joshi, lead author of the paper, joins us to share how gRNAde is speeding up RNA-based medicines and programmable biology.

What if aging itself is the disease we should be curing? In this episode, I sit down with Aubrey de Grey, the legendary biogerontologist who has spent decades arguing that aging is not an inevitable fate but an engineering problem with solvable components. We dive into the science behind his SENS framework, explore why the longevity field is finally gaining mainstream momentum, and debate just how close we are to adding decades of healthy life to the human lifespan. Whether you're a skeptic or a true believer, this conversation will challenge how you think about mortality, medicine, and what it means to grow old. Aubrey is also someone that I admire deeply, so I hope you find this conversation interesting!

Antibody design is one of the most exciting challenges in AI drug discovery. After Alphafold solved many of the problems of protein structure prediction, researchers moved their attention to protein structure design, and antibodies in particular are one of the most interesting proteins that we would like to design. Both because of the impact in patients as well as massive commercial potential. Join my chat with Santiago Mille from Stanford University about Germinal, a novel pipeline for antibody design.

In this episode, I sit down with Dr. Maria Marinova to uncover one of the most misunderstood frontiers in human biology: female reproductive aging. We break down why female fertility declines, what’s actually happening at the cellular level, and the emerging science that suggests this decline may be reversible. Not someday in the distant future, but now.

Matt Kaeberlein is one of the world’s leading scientists in aging biology. He is a biogerontologist with 250+ publications, former University of Washington professor, and co-founder of landmark initiatives like the Dog Aging Project. In this episode, we dive into the real mechanisms of aging, how scientific discovery actually happens, where longevity research is going next, and why much of what people believe about “anti-aging” is wrong. If you’re interested in living longer, staying healthier, or understanding the future of biomedical science, this conversation will challenge your assumptions and give you a clearer view of what the next decade of longevity research might actually look like.

Is protein folding solved? Not quite, even though the progress has been tremendous since the first AlphaFold and up to last year's Nobel prize. The team behind Boltz and Boltz-2, from MIT CSAIL and Jameel Clinic, just released Boltzgen, a state of the art model for protein design. In this chat with Gabriele Corso I review the progress in the field and whats next.

Shantanu Singh is one of the principal investigators at the celebrated Broad Institute of MIT and Harvard. His research is centered around finding “fingerprints” of genes, chemicals and diseases from microscopy images of cells. Which has tremendous applications for drug discovery and curing diseases. I hope you enjoy this episode! Also check out some more links about his work below: About the Lab: - Carpenter-Singh Lab: https://carpenter-singh-lab.broadinstitute.org/ - MIT Technology Review article on Cell Painting / JUMP Consortium: https://www.technologyreview.com/2023/03/03/1069261/a-technique-called-cell-painting-could-speed-drug-discovery/ - Recent review of Cell Painting applications: https://rdcu.be/d2vHH Resources: - Cell Painting Gallery (open image datasets): https://www.nature.com/articles/s41592-024-02399-z - OASIS Consortium (liver toxicity prediction and reducing animal testing): https://oasisconsortium.org/ Additional Reading: - On our two-PI lab model: https://www.asbmb.org/asbmb-today/people/083122/high-affinity-binding

Andy and his team at Vincere have been doing amazing work over years to figure out the mitochondrial mechanisms that may contribute to Parkinson's and other neurodegenerative diseases. Listen in as we discuss curing Parkinson's, using AI to find new molecules and broader drug discovery.

Andrew White and his team at Future House have one of the most ambitious missions. I'll quote here because I couldn't say it better myself: Our mission is to build an AI scientist, or AI systems, that can automate scientific research and accelerate the pace of discovery, so humanity can find cures for disease, solutions for climate change, and other species-accelerating technologies. Must watch! 👀

What if the biggest breakthroughs in health and biotechnology aren’t waiting on new ideas but on better experiments? In this episode, Michael Florea joins Javier to expose the hidden bottlenecks in animal research, the quiet revolution of automation in the lab, and the radical possibilities of treating DNA itself as medicine. This conversation peels back the curtain on how science really moves forward and why the future of drug development may look nothing like today.

Join my conversation with Matthew "Oki" O'Connor Co-CEO of Cyclarity Therapeutics. We talk about curing cardiovascular disease, radically extending healthy longevity and the drug discovery journey.

Nicholas Runcie of Oxford University and I discuss whether large language models such as ChatGPT can really understand chemistry. Which of course will be essential as we try to use them to find new medicines and materials.

Eva Smorodina, researcher at the University of Oslo and expert in Computational Chemistry, joins me for an interesting conversation about designing antibodies, tools for biology and the future of AI and drug discovery. I hope you will enjoy!

In this episode I talk with the amazing Reason and Mourad from Repair Bio about a cure for cardiovascular disease. Reason serves as CEO and is also a legend in the world of longevity, having run https://www.fightaging.org for a couple of decades. Mourad serves as CSO and is a celebrated researcher with stints at Harvard Medical School and Pfizer.

Google recently announced AI Co-Scientist, a state-of-the-art AI agent turbo-charging research. The Co-Scientist team has already uncovered new liver-fibrosis targets and repurposed drugs for cancer. Don't miss this episode with Vivek Natarajan, Research Lead for Google’s AI Co-Scientist!