From First Principles

Hosted by Lester Nare and Krishna Choudhary, this episode marks Krishna’s return to the studio after paternity leave — and the timing could not be more fitting. Today’s deep dive is about inheritance: not just the classic Mendelian rules most of us learned in biology class, but the stranger, more dynamic world of non-Mendelian epigenetic inheritance.
Starting from Gregor Mendel and his pea plants, Lester and Krishna rebuild the foundations of genetics from first principles: dominant and recessive alleles, Punnett squares, chromosomes, fruit flies, DNA, and the physical mechanism behind inherited traits. Then they move into the “software layer” of biology: epigenetics, DNA methylation, chromatin packaging, RNA interference, and paramutation — cases where the genetic code is present, but the cell’s machinery silences or rewrites how that code is used.
The episode centers on a new Nature Genetics paper, “Non-Mendelian inheritance of DNA methylation patterns in mice,” which suggests that non-Mendelian epigenetic inheritance may be more widespread in mammals than previously understood. The conversation also covers why Oxford Nanopore sequencing made this kind of analysis possible, why methylation patterns can be hard to trace across generations, and what all of this could mean for disease risk, drug response, sex differences, evolution, and the long-running nature-versus-nurture debate.

Summary
Mendel’s rules — how pea plants, true-breeding lines, dominant and recessive traits, and Punnett squares gave us the first mathematical laws of inheritance.
The first cracks in Mendel — how chromosomes, fruit flies, sex-linked traits, and linked genes showed that inheritance is more complicated than independent assortment.
DNA as hardware, epigenetics as software — why having a gene is not the same thing as expressing it, and how methylation and chromatin packaging can silence parts of the genome.
Paramutation — how one allele can change the expression state of another allele across generations, creating inheritance patterns that do not follow standard Mendelian expectations.
Oxford Nanopore and the technology shift — why long-read sequencing and direct methylation detection make it possible to trace epigenetic marks back to the parent they came from.
The mouse methylation paper — how researchers used collaborative cross mice to show that most methylation inheritance looks Mendelian, but a meaningful fraction appears to follow stranger non-Mendelian rules.
Why it matters — potential implications for clinical genetics, disease risk, drug efficacy, sex-specific biology, and the relationship between nature and nurture.
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Hosted by Lester Nare and Krishna Choudhary, this episode is the second interview in our ongoing collaboration series with Carnegie Observatories. Krishna sits down with Dr. Michael Blanton, the new Director of the Carnegie Observatories, for a wide-ranging conversation on how astronomy became one of the most data-rich sciences, how the Sloan Digital Sky Survey helped change the culture around open data, what the next era of astronomical data science and AI could look like, and one of the galaxy mysteries Blanton still wants to solve: why the most massive galaxies in the universe stop forming stars.The conversation starts with Blanton’s Princeton roots and his work connected to the Sloan Digital Sky Survey, then moves into the culture of public astronomical data, the NYU Value-Added Galaxy Catalog, Vera Rubin Observatory, Carnegie’s role in the future of astronomy, the Magellan telescopes, astronomical archives, MaNGA and eBOSS, galaxy formation, dark matter, and even the science behind the black hole visualizations in Interstellar.Audio note: this was one of our first out-of-studio interviews, and there are a few minor audio issues in parts of the conversation. We appreciate your patience, and we’ll be better prepared for future field interviews.Also, if you’re in Los Angeles, Krishna will be giving a talk at Exploring Physics at UCLA, hosted by UCLA’s physics outreach organization Continuum, on Saturday, June 6 at the Fowler Museum. His talk runs from 9:30–10:30 AM.Register here: https://luma.com/3al1hj5h

Hosted by Lester Nare, this episode features astrophysicist Dan Gilman for a deep conversation on one of the biggest open questions in modern physics: what dark matter actually is. Starting from first principles, Lester and Dan walk through why the evidence for dark matter is now so strong, how strong gravitational lensing works, why tiny distortions in lensed light can reveal invisible clumps of matter, and how the next generation of surveys may transform the field. Krishna is out on family leave for this one, but the conversation stays fully in the From First Principles lane: grounded, visual, and science-first.
Summary
What dark matter is — Dan explains the basic case for dark matter, why it appears to interact only through gravity, and why multiple independent observations now point to the same conclusion.
How strong gravitational lensing helps — the episode uses intuitive analogies like tides, fish tanks, and flashlights to explain how astronomers can infer the presence and structure of dark matter without seeing it directly.
What Dan actually studies — the core of Dan’s work is building and testing simulations of lensed systems to see which dark matter theories best match reality.
Why the next few years matter — Rubin, Roman, Euclid, and AI-assisted lens finding could dramatically increase the number of usable lens systems and sharpen the search for dark matter’s fundamental nature.
Show Notes
Dan Gilman on strong gravitational lensing and dark matter substructure
Euclid mission overview
Rubin Observatory overview
Roman Space Telescope mission context

Hosted by Lester Nare and Krishna Choudhary, this interview features John Mulchaey, the 12th President of Carnegie Science and former Director of the Carnegie Observatories. The conversation starts with his early work on galaxy groups and dark matter, then expands into how Carnegie works as a scientific institution, what the Giant Magellan Telescope could unlock for exoplanets and astronomy, how science funding actually works, and why eclipse chasing is still one of the most magical experiences in science.
Summary
Galaxy groups and dark matter — Mulchaey explains why small galaxy groups matter more than most people realize, and how X-ray observations of hot gas helped make their masses measurable.
Carnegie’s model — the interview gets into what makes Carnegie unusual: scientific freedom, long time horizons, and room to pursue surprising questions.
The Giant Magellan Telescope — a look at why bigger telescopes matter, what GMT changes, and why exoplanet atmospheres are one of the biggest goals ahead.
The bigger picture — science funding, philanthropy, how astronomy has changed, and why total solar eclipses still inspire so many astronomers.
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Show NotesJohn Mulchaey leadership bio — Carnegie Sciencehttps://carnegiescience.edu/about/leadershipCarnegie Science appoints John Mulchaey as its 12th Presidenthttps://carnegiescience.edu/news/carnegie-science-appoints-john-mulchaey-its-12th-presidentGiant Magellan Telescope — official overviewhttps://giantmagellan.org/about-us/1993 NASA write-up on Mulchaey’s dark matter result in galaxy groupshttps://science.nasa.gov/missions/hubble/dark-matter-found-in-a-typical-cluster-of-galaxies/Carnegie Science Great North American Eclipse outreach recaphttps://carnegiescience.edu/yearbook/2024/science/great-north-american-eclipsePerot Museum eclipse partnership recaphttps://www.perotmuseum.org/events/solar-eclipses/

Hosted by Lester Nare and Krishna Choudhary, this rundown episode covers four new science stories at a high level: a huge new 3D ant imaging database built with synchrotron X-ray microtomography, a lunar agriculture experiment that grew chickpeas in simulated moon soil using fungi and worm waste, AI-assisted discovery of strange objects in the Hubble archive, and a new programmatic roadmap for room-temperature superconductivity. There is also another round of Are You Smarter Than a Scientist? in the middle.

Summary

Particle accelerators meet biodiversity — researchers built a massive high-resolution ant imaging resource, covering nearly 800 species and thousands of specimens, with AI-assisted 3D reconstruction.

Moon farming gets weird — chickpeas were grown in lunar regolith simulant with help from mycorrhizal fungi and worm-derived compost, a first step toward sustainable off-world agriculture.

AI found hidden anomalies in Hubble’s archive — AnomalyMatch sifted through roughly 100 million source cutouts in just days and surfaced new candidate lenses, mergers, and other rare objects.

The superconductivity long game — a new PNAS perspective argues that room-temperature superconductivity is not ruled out by physics, and calls for a coordinated push to get there.
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Show Notes
High-throughput phenomics of global ant biodiversity — Nature Methods
Bioremediation of lunar regolith simulant through mycorrhizal fungi and plant symbioses enables chickpea to seed — Scientific Reports
Identifying astrophysical anomalies in 99.6 million source cutouts from the Hubble legacy archive using AnomalyMatch — Astronomy & Astrophysics
The path to room-temperature superconductivity: A programmatic approach — PNAS