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