Today in @ScienceMagazine we report how lipids specialize for life under the crushing pressures of the deep sea and what this means more broadly for the composition of cell membranes (1/n)

This has been one of my favorite projects - it taught me so much about sterols, their metabolism, and the hoops cells go through to make their lipids dance in just the right away. Support from @NSF @NIH (n/n).

The simulations told us how small chemical mods across the pathway altered the conformations of the sterols (TLDR it's about the tail). Perhaps even more profoundly, they suggest what it might really take to make a domain that stays fluid. See vid:

We then collaborated with sterol expert Alex Sodt at @NICHD_NIH and his postdoc Laura Lopes Jacobs who built all-atom models for eqch intermediates. We were floored by how well their sims predicted key experimental results, like ordering of DMPC membranes

Turns out the pathway needs to balance it's capacity to order lipids to get to fluid domains, and makes a series of modifications (a methylation, addition and subtraction of double bonds) to hit just the right sweet spot.

Israel found that the pathway builds up to Lo (liquid) domains. Bud it does not do so monotonically: early sterols support domains but they are solid (bad for life). Then domain capacity vanishes. Then right at the end it returns - but now the domains are fluid and functional.

Brave and driven PhD student Israel Juarez-Contreras made every conceivable Erg mutant to generate strains that accumulate each sterol in the pathway, and even some that are not. This allowed him to do a systematic analysis both in love yeast and (once extracted) in liposomes.

We wanted to test the Bloch hypothesis in the context of this function. We turned to yeast cells both because of their wonderful genetics but also because their vacuoles mebranes phase seperates into large domains that depend on sterols, just like giant liposomes!

Bloch's hypothesis preceded discovery for another function of sterols: to form Lo phases with saturated phospholipids that form discrete domains, yet are fluid. See seminal work by Keller, Feigenson, London, and many others using synthetic liposomes.

Sterols like ergosterol or cholesterol are the most abundant lipids in eukaryotic cells. Yet they are made from very long synthetic routes. Why? Konrad Bloch @MCB_Harvard proposed ~50 years ago that the pathways must continuously shape the sterol to better order phospholipids

In @ScienceAdvances, we report how small chemical modifications in the metabolism of ergosterol are needed for yeast membranes to phase seperate into ordered yet fluid domains (1/n).

New piece in Journal of Cell Science on the origin and evolution of mitochondrial inner membrane structure and composition #lipidtime @Co_Biologists.

RT @LabFriedman: Be sure to mark your calendars for March 26th at 12pm ET for the @AsbmbLrd seminar series. We have two great mitochondria-….

RT @Nature: Nature research paper: RNA control of reverse transcription in a diversity-generating retroelement.

RT @NaamaAviram: Thank you to the @RNASociety for featuring me in the spotlight! .In the interview, I reflect on my path in science, the me….

Thrilled to be part of this cohort with such a great group of other biophysicists and cell biologists @cohenlaboratory @cjobara #lipidtime.

Spotted in the @mgreenberglab at @waynestate 🫡

RT @RobertoJBrea: Delighted to share our latest work “Protocells by spontaneous reaction of cysteine with short-chain thioesters” published….

Finally recovered from almost a week in beautiful Ithaca giving a @CornellChem seminar, collecting data with @CHESS_user, and seeing all my old haunts. Thanks @AndoLab @basktastic for hosting me 🍁🍂🍃

New review at @jlipidres on the nexus we see between mitochondrial lipid metabolism and biophysics, with a focus on lipid curvature

Epic autumnal-ness (and science) at @dartmouth last week. Thanks @Emily_L_Behrman for the invite!