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Freddy Benning @fmcbenning.bsky.social · 23/06/2025

10/💰 This study was made possible by funding from the NIH, CIHR, CFI, NSERC, NFRF, HHWF, @moorefound.bsky.social @simonsfoundation.org @snsf.ch 🇺🇸🇨🇦🇨🇭

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Freddy Benning @fmcbenning.bsky.social · 23/06/2025

9/ 📣 This was a wonderful collaboration with the daCosta Lab at @uottawa.ca. A big shout-out to my 🦋-less co-firsts Melody Nguyen and Tristan Bell and to all co-authors. @lukechao.bsky.social Thanks to the HMS EM facility, HMS MIcRoN, and the MIT.nano cryo-EM facility for their support.

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Freddy Benning @fmcbenning.bsky.social · 23/06/2025

8/🎯 Our observations reflect a lack of correlation between respiratory function and cristae attachment. Instead, we observe other morphological cristae defects associated with compromised respiration. By identifying functional key residues, this work paves the way for future mechanistic studies.

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Freddy Benning @fmcbenning.bsky.social · 23/06/2025

7/🔬 Using TEM, cryo-ET and fluorescence microscopy, we describe a phenotype that is specific to a mutant of these four ASR-identified residues, which features box-like shaped cristae and longer average cristae lengths.

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Freddy Benning @fmcbenning.bsky.social · 23/06/2025

6/🔬 Several TEM studies have shown that Mic60 and Mitofilin deletions result in detached cristae. We observe the same phenotype for our knockout variants. ✅ 🤯 Surprisingly, Mitofilin ancestors which rescue respiratory growth like wildtype have knockout-like detached cristae.

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Freddy Benning @fmcbenning.bsky.social · 23/06/2025

5/🎯 Comparing reconstructed ancestors, we identified four residues in the Mitofilin domain that are sufficient for rescuing respiration.

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Freddy Benning @fmcbenning.bsky.social · 23/06/2025

4/🧫 We found that common Mitofilin ancestors as far back as the putative last opisthokont common ancestor #LOCA rescues respiration in yeast. ✅

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Freddy Benning @fmcbenning.bsky.social · 23/06/2025

3/❓How did Mitofilin-supported respiration diverge between yeast 🍺 and humans 👤? 💻🦖🧪 We used ancestral sequence reconstruction #ASR to reconstruct ancestral Mitofilin sequences and resurrected them for in vivo characterization.

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Freddy Benning @fmcbenning.bsky.social · 23/06/2025

2/ 🧫 Using respiratory growth assays, we found that swapping the yeast Mitofilin domain with that of another yeast rescued respiration. ✅ Replacing it with human or bacterial homologues at the endogenous locus did not rescue respiration. 💀 ❗This is in contrast to previous plasmid-based work.

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Freddy Benning @fmcbenning.bsky.social · 23/06/2025

1/ ❓Mic60, a core component of the #MICOS complex in the #mitochondrial inner membrane, is crucial for the organization of #cristae and their functions. It's unclear, how Mic60's #Mitofilin domain encodes cristae-supported functions like cellular respiration.

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Freddy Benning @fmcbenning.bsky.social · 23/06/2025

Out in print! Using ancestral sequence reconstruction 🦖, in vivo characterization, and 🔬 analysis, we identified key residues in the mitochondrial protein #Mic60 that affect #respiration in #yeast. Since the preprint, we added some cool findings. 🧵⬇️ onlinelibrary.wiley.com/doi/10.1002/...

onlinelibrary.wiley.com

Ancestral sequence reconstruction of the Mic60 Mitofilin domain reveals residues supporting respiration in yeast

In eukaryotes, cellular respiration takes place in the cristae of mitochondria. The mitochondrial inner membrane protein Mic60, a core component of the mitochondrial contact site and cristae organizi...

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Freddy Benning @fmcbenning.bsky.social · 16/05/2025

I’m thrilled to share that I will join @stowersinstitute.bsky.social this fall to explore the evolution and design of bioenergetic membranes in bacteria.

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Reposted by Freddy Benning

Stowers Institute @stowersinstitute.bsky.social · 15/05/2025

We’re proud to welcome two bold scientific minds to the Institute! Arvind Pillai, PhD, joins as Assistant Investigator exploring protein #evolution and design. Friederike Benning, PhD, joins as Stowers Fellow studying membrane complexity in #bacteria. Read more: bit.ly/3SCZQiM

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Reposted by Freddy Benning

Paula Navarro @navarropaula.bsky.social · 03/04/2025

🚨👉 Please check our recent work on bacterial cell division. In situ Cryo-ET reveals the cellular function of the penicillin binding protein 1b supported by AFM, live-cell imaging, in silico AlphaFold proteome screen and TIRFM. Hope you enjoy the read! #teamtomo #cryo-ET ❄️🔬🐎 big thanks to the team!

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Reposted by Freddy Benning

Ben Kleinstiver @bkleinstiver.bsky.social · 13/03/2025

Interested in learning more about genome editing tool dev & their application to treat human diseases? 🧬 🏥 We're hiring graduating seniors who are seeking ~2 years of post-bac research experience. If you're interested in gaining experience in next gen medicines, please reach out and apply! Link 👇

massgeneralbrigham.wd1.myworkdayjobs.com

Research Technician I - Center for Genomic Medicine

Site: The General Hospital Corporation At Mass General Brigham, we know it takes a surprising range of talented professionals to advance our mission—from doctors, nurses, business people and tech expe...

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Freddy Benning @fmcbenning.bsky.social · 08/01/2024

A big shout-out to my incredible team mates Simon Jenni, Coby Garcia, Melody Nguyen, Xuewu Zhang and @lukechao.bsky.social

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Freddy Benning @fmcbenning.bsky.social · 08/01/2024

How do baculoviruses protect their genome? Delighted to present our findings in print! We use cryo-EM to determine the structure of a baculoviral nucleocapsid. We show how the tiny capsid protein VP39 assembles into a giant nucleocapsid.❄️🔬 www.nature.com/articles/s41...

nature.com

Helical reconstruction of VP39 reveals principles for baculovirus nucleocapsid assembly - Nature Com...

Baculoviruses are used as insecticides, gene therapy tools, and protein production vectors. Here, the authors report the structure of the Autographa californica MNPV nucleocapsid and its fold conserva...

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