Mukund Thattai

Mukund Thattai

@thattai.bsky.social

Physicist fascinated by biology, trying to understand how cells work. Also: public engagement, science and culture, puzzles.

608 followers237 following76 posts

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My most prized possession, and my deepest regret. Carl Sagan is the reason I became a scientist, it was a dream come true to be accepted into his class. But he was suffering from cancer, and unable to teach. I never met him. He died a year later, aged 62. Sagan would have been 90 this November.

To be a mathematician now is to know a world the rest of us will soon inhabit. This podcast was unexpected, surprising, heart-wrenching, yet ultimately uplifting. Listen.

Steven Strogatz@stevenstrogatz.com

I spoke with The Daily about what’s happening to mathematics in the age of AI—and what it feels like to be a mathematician right now. The conversation went places I hadn’t expected. Thank you to Rachel Abrams, Annie Minoff, and their team. www.nytimes.com/2026/10/13/p...

GAMX is a day-long event featuring new tabletop games by Indian creators: 3 Oct, 10am - 9pm, Bangalore. I'll show my new game - Swalpa Adjust Maadi! - where you dig up Bangalore roads to cut off power and water from your opponents! Entry is free! We need feedback, come and try out the games.

Model collapse (AI fed on its own slop will eventually revert to a fixed distribution) is easy to explain - this is exactly what happens during audio feedback: a mic amplifies the output of the mechanical speaker instead of the human speaker. The result is a single frequency, instead of music.

Rather than taking on wingnuts and alien conspiracies, we should do the harder job of confronting the entrenched molecule-centric view of biology, one which conditions students to use precisely such reductionist language to describe the "functions" of genes in their talks, papers and theses.

Simon Fisher@profsimonfisher.bsky.social

25 years ago, we implicated rare variants of the FOXP2 gene in a severe speech disorder. I’ve spent much time stressing that FOXP2, while interesting, is not the mythical “gene for language”. Weirdly, on occasion I also need to explain why it’s not “proof of aliens”. Full disclosure in this 🧵. 1/n 🧪

Mukund Thattai reposted

This will be on 26 June in Paris! 🤩You are welcome to join and participate in this exciting 1-day conference at the College de France on Biological computational accross areas of biology. Fantastic speakers. Free, no registration, at the heart of Paris on a lovely season. Worth planning a weekend…?

Thomas Lecuit@thomaslecuit.bsky.social

Here is the announcement of a Symposium @college-de-france.fr on 26 June on Information Flow and Computation in Biological systems. A great line of speakers on a variety of topics from embryogenesis to neuroscience, immunology and microbiology. Free entrance, come if you are in Paris end of June 🤩

Mukund Thattai reposted

1/35 New preprint! We show that obligate multicellularity removes fundamental population genetic barriers to multicellular adaptation. Even a brief unicellular phase can dramatically constrain the evolution of beneficial multicellular traits. www.biorxiv.org/content/10.6...

biorxiv.orgObligate multicellularity circumvents population genetic barriers to collective-level adaptationComplex multicellularity has evolved in just five lineages (animals, plants, brown algae, red algae, and fungi) and in each case, these organisms develop clonally and are obligately multicellular. While prior work has shown that clonal development plays a critical role in the evolution of complex multicellularity, none has disentangled this from the impact of obligate vs facultative multicellular life cycles. Here we use experimental evolution with engineered snowflake yeast ( Saccharomyces cerevisiae ) to directly test how life cycle structure affects multicellular adaptation. We created isogenic strains capable of switching between unicellular and clonal multicellular phases, then evolved populations for 192 days under obligately multicellular, facultatively multicellular, and obligately unicellular regimes. Obligately multicellular populations rapidly evolved larger size, primarily driven by a whole genome duplication, in all five replicates. Facultative populations showed dramatically constrained evolution, with tetraploidy evolving in only 2/10 facultative populations despite experiments demonstrating that it is strongly beneficial across the full life cycle. Mathematical modeling reveals the mechanistic basis for this constraint: facultative life cycles create establishment barriers through two population genetic effects. Group formation dramatically reduces the number of units of selection, making beneficial multicellular mutations vulnerable to drift. This asymmetry in population size between life cycle phases also allows cell-level selection to overpower group-level selection, eliminating mutations that provide group-level benefits but carry cell-level costs. These findings demonstrate that obligate multicellularity circumvents fundamental population genetic barriers to collective-level adaptation, helping explain why complex multicellularity has evolved exclusively in obligately multicellular lineages, and suggesting similar constraints may operate in other evolutionary transitions in individuality. ### Competing Interest Statement The authors have declared no competing interest. U.S. National Science Foundation, https://ror.org/021nxhr62, DEB-1845363 Howard Hughes Medical Institute Gilliam Fellowship National Science Foundation Graduate Research Fellowship

Mukund Thattai reposted

Replying to @thattai.bsky.social

Lynn did acknowledge these earlier authors (e.g., Merechowsky, Wallin), though, in her 1967 paper. "...these ideas are not new..." This is often overlooked, both by people who claim that she "stole" these ideas, as well as those who claim that she didn't become aware of them until later.

The origin story of eukaryotes has more plot twists than a Hollywood blockbuster! 🧵 Read more in my new review: doi.org/10.1146/annu.... Only in the 1960s were the terms "prokaryote" and "eukaryote" formalized! As originally defined, eukaryotes had complex architectures, prokaryotes did not.

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The "tubules-first model" suggests Asgard archaea should have internal membranes. Do they? Just as our review was being proofed, the Baum lab reported that the Asgard Y. umbracryptum has heterogeneous internal membranes! It's not yet clear which proteins regulate their formation.

Many mysteries remain. Central among these: both the lipids and viruses of modern eukaryotes are derived from bacteria, not archaea. This requires explanation. Experiments on new model organisms bring us closer than ever to answering these questions. A great time to do evolutionary cell biology!

The origin story of eukaryotes has more plot twists than a Hollywood blockbuster! 🧵 Read more in my new review: doi.org/10.1146/annu.... Only in the 1960s were the terms "prokaryote" and "eukaryote" formalized! As originally defined, eukaryotes had complex architectures, prokaryotes did not.

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Asgard archaea express proteins otherwise found only in eukaryotes. These "eukaryotic signature proteins" include many related to modern membrane traffic machinery. But "coatomers" like clathrin, COPI and COPII that generate vesicles in eukaryotes are absent. What were the ancestral cargo carriers?

Exciting new studies show that Asgard proteins do remodel membranes. In fact, Asgard machinery can support every step in tubule formation. This is the basis of the "tubules-first model" for the origin of eukaryotic membrane traffic: tubular carriers may have emerged before spherical coated vesicles.

The origin story of eukaryotes has more plot twists than a Hollywood blockbuster! 🧵 Read more in my new review: doi.org/10.1146/annu.... Only in the 1960s were the terms "prokaryote" and "eukaryote" formalized! As originally defined, eukaryotes had complex architectures, prokaryotes did not.

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Fleshing out this model: an ancestral Asgard archaeon eventually engulfs an alphaproteobacterium. This results in endosymbiotic mitochondria, as well as the first endomembrane with its own lumen. This endomembrane is the proto-endoplasmic reticulum, a portion of which is the nuclear envelope.

But this proto-eukaryote is still missing many features of modern eukaryotic cells. Where did the endomembrane compartments other than the ER, like the Golgi apparatus, endosomes and lysosomes, come from? How did the system of carriers ferrying cargo between these compartments arise?

The origin story of eukaryotes has more plot twists than a Hollywood blockbuster! 🧵 Read more in my new review: doi.org/10.1146/annu.... Only in the 1960s were the terms "prokaryote" and "eukaryote" formalized! As originally defined, eukaryotes had complex architectures, prokaryotes did not.

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At the same time, Buzz and David Baum put forward their inside-out hypothesis for the origin of eukaryotes. In this model, an ancestral archaeon has surface protrusions that increase contact area with symbiotic bacteria. These protrusions eventually engulf the bacteria, which become mitochondria.

It would take five more years for an Asgard archaeon to be grown in a lab by Imachi and colleagues (with a doubling time of 14-25 days!). Amazingly, these cells have elaborate surface protrusions supported by actin-like filaments, reminiscent of the archaeal host in the inside-out model.

The origin story of eukaryotes has more plot twists than a Hollywood blockbuster! 🧵 Read more in my new review: doi.org/10.1146/annu.... Only in the 1960s were the terms "prokaryote" and "eukaryote" formalized! As originally defined, eukaryotes had complex architectures, prokaryotes did not.

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Modern sequence data shows that eukaryotes are chimeras of the two prokaryotic groups! Our metabolic genes have bacterial origins, our DNA replication, transcription and translation genes (including rRNA) have archaeal origins. But which present-day bacteria and archaea are our closest relatives?

In 2015 Ettema and colleagues report that sediments from Loki's Castle (a field of deep sea hydrothermal vents near Iceland) contain DNA from a previously unknown archaeal group, closely related to eukaryotes. These "Lokiarchaeota" are the first known members of the Asgard archaea.

The origin story of eukaryotes has more plot twists than a Hollywood blockbuster! 🧵 Read more in my new review: doi.org/10.1146/annu.... Only in the 1960s were the terms "prokaryote" and "eukaryote" formalized! As originally defined, eukaryotes had complex architectures, prokaryotes did not.

In 1967 Lynn Margulis argued that mitochondria were once free-living bacteria, symbiotically acquired by a host cell. Similar ideas had been proposed in the early 20th century, but Margulis came to them independently. Her influential paper was rejected by fifteen journals before being published.

In the 1970s, Carl Woese used ribosomal RNA sequences to classify all of life for the first time. Prokaryotes broke into two: the bacteria, and a previously unknown group, christened the archaea! rRNA sequences suggested eukaryotes were more similar to archaea. But this turned out to be misleading.

Out now in @annualreviews.bsky.social: my review on the origins of eukaryotic membrane traffic! I propose that archaea-derived proteins supported a primordial system of tubules to ferry cargo between compartments. Modern coated vesicles may have been a later innovation. doi.org/10.1146/annu...

doi.orgA Tubules-First Model for the Origin of Eukaryotic Membrane TrafficThe discovery of membrane trafficking proteins in Asgard archaea—the closest archaeal relatives of eukaryotes—reveals the deep evolutionary roots of the eukaryotic endomembrane system. This review syn...

Mukund Thattai reposted

Here is the announcement of a Symposium @college-de-france.fr on 26 June on Information Flow and Computation in Biological systems. A great line of speakers on a variety of topics from embryogenesis to neuroscience, immunology and microbiology. Free entrance, come if you are in Paris end of June 🤩

Excited to visit the @alleninstitute.org for the Lake Conference on Emergence and Self-Organization: lakeconferences.org/conf/17d01bb... I'll speak about Affordance Theory, pioneered by JJ Gibson in the 1970s. We use this framework to explore the evolution of eukaryotic endomembranes (see 🧵 below).

lakeconferences.orgConference - Modeling Life from Cells to Tissues: Emergence and Self-Organization - Lake Conferences
Mukund Thattai@thattai.bsky.social

How did eukaryotic cells get their Golgi, endosomes, lysosomes and other endomembrane compartments? We show that endomembrane evolution depends on long periods of neutral molecular exploration, punctuated by sudden leaps. New preprint: www.biorxiv.org/content/10.6...

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This is the amazing PhD work of my student Sahana Shridhar, who is also responsible for the beautiful figures. Also, this project would not have been possible without Kritika Kumari, who was able to massively speed up our computations during her year interning in our lab. Do send us your comments!

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The only evolutionary moves we allow are gene duplication, deletion, and simple mutations. We show that these are sufficient to convert simple endomembrane systems into more complex ones.

We construct an entire evolutionary landscape, starting from a simple proto-eukaryotic system and moving up through a hierarchy functional complexity. Each transition in this landscape backed up by an explicit series of molecular mutations.

We do this by computationally exploring billions of possible endomembrane systems. We find that systems allowed by molecular rules are extremely rare. So how can evolution search this sparse space to discover complex endomembrane configurations?

Mukund Thattai reposted

Protocells from three inorganic salts, some formaldehyde and water? They grow? They synthesise organic molecules of core biomolecular classes: amino acids, sugars, lipid-like motifs? And, there are similar structures in today's oceans? Yes! Read on. arxiv.org/abs/2601.11013

arxiv.orgDe novo emergence of metabolically active protocellsA continuous route from a disordered soup of simple chemical feedstocks to a functional protocell -- a compartment that metabolizes, grows, and propagates -- remains elusive. Here, we show that a homo...

Gutting the humanities will not save the sciences. This piece is worth reflecting on: "The broad liberal arts education Carl Sagan received at the University of Chicago played an important role in his development as a scientist and intellectual." www.loc.gov/collections/...

loc.govloc.gov

the crisis in which the University of Chicago is now engulfed -- one entirely of its own making, and which has led to the (hopefully temporary) suspension of admissions into numerous PhD programs in the humanities -- represents I think a seismic event in the history of American higher education 1/

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Asgard archaeal genomes encode many eukaryotic signature proteins, previously thought to be restricted to eukaryotes. In modern eukaryotes several of these ESPs are involved in membrane traffic. But Asgard archaea lack canonical vesicle coats. So what were these proteins doing in FECA?

A closer look shows that in present-day eukaryotes these Asgard ESPs are involved in the generation of tubular carriers at the ER, endosomes/TGN, and at the plasma membrane. In the review I discuss several new studies showing that Asgard versions of these proteins can indeed generate tubules!

Eukaryotes arose via a merger between archaea and bacteria, with eukaryotic traits emerging gradually on the path from FECA (the archaeal first eukaryotic common ancestor) to LECA (last eukaryotic common ancestor). What if FECA was already an atypical archaeon with rudimentary eukaryote-like traits?