Segmenting cryo-electron tomography data: Extracting models from cellular landscapes Cryo-electron tomography provides an unprecedented view of cellular architecture, yet extracting meaningful biological insights remains challenging. S…

I have lots of opinions—but for your sake, I’ve limited them to segmentation in cryo-ET for this article 😉
www.sciencedirect.com/science/arti...

#teamtomo

🚨New preprint!🚨 #teamtomo
We expanded Surface Morphometrics to quantify membrane thickness from cryo-ET—revealing local variation across organelles.

Led by the lab’s first grad student, @mmedina300kv.bsky.social (defending Monday! 🍾) w/ @attychang.bsky.social @hamid13r.bsky.social & @tomo.science

Advances in uncovering the mechanisms of macromolecular conformational entropy - Nature Chemical Biology Protein conformational entropy plays a vital role in functions like binding and catalysis. This Perspective discusses three ways macromolecules use conformational entropy: prepaying entropic costs, re...

A Perspective by @stephanieaw.bsky.social and @fraserlab.com discusses ways macromolecules use conformational entropy to control binding, catalysis, and allostery

www.nature.com/articles/s41...

Arzeda Awarded DARPA Funding to Advance AI-Driven Protein Design for National Security /PRNewswire/ -- Arzeda, the industry-leading Protein Design Company™, today announced it has been selected for an award from the Defense Advanced Research...

Arzeda has been awarded DARPA funding to advance AI-driven protein design—even with limited data! We're pushing the boundaries to create next-gen proteins for national security, sustainability, and beyond. #AI #ProteinDesign
www.prnewswire.com/news-release...

Example series showing the surface morphometrics workflow

Tomorrow(!) morning at 9AM pacific, I am giving a webinar for EMS discussing the surface morphometrics pipeline and our approach to contextual structural biology #teamtomo. Free to attend, hope to see you all there!

us06web.zoom.us/webinar/regi...

The human mitochondrial ClpXP is uniquely assembled and regulated compared to its bacterial counterparts. Congrats to Kelly Chen on her years of hard work on this challenging complex!

www.biorxiv.org/content/10.1...

Come be my colleague! UW Tacoma is hiring an Assistant Professor of Biochemistry. We're looking for someone excited about mentoring undergraduates in research, inclusive teaching, and being part of an interdisciplinary community of scholars. apply.interfolio.com/154390

The Barad lab is hiring across all levels. Open positions here: baradlab.com/join/. If you are interested in doing cutting edge tomography and computational methods development to study intracellular bacterial infection, and living in Portland, OR, but don't fit the openings, reach out anyway!

I'm immensely grateful for Gabe's mentorship throughout my postdoc, and for our colleagues at Scripps, especially the Kelly and Forli labs.

We hope our study can further the understanding of TTR's rich biological role, as well as bolster the relevance of structural studies to probe the paramount role of protein dynamics, even in the age of fast and accurate protein structure prediction.

The partially unfolded state we observe is also consistent with amyloid formation intermediates proposed to exist more than 30 years ago, and provides possible explanation to how certain common mutations lead to TTR amyloidosis.

We think the loss of entropy (ie, the partially unfolded state) in the double-bound state explains TTR's negative cooperativity.

We also found that when both binding sites are occupied, the partially unfolded state seems to disappear. When only one of the binding sites is occupied, the partially unfolded state comes back.

We started by looking at apo TTR, and found multiple conformations indicating TTR can go a sort of accordion motion and partial unfolding (beta sandwich "fraying").

All this work was carried out in a 200keV Arctica, on gold-substrate grids coated with a single layer of graphene. This support was crucial to maintain the integrity of the sample.

BONUS: TTR is a D2 tetramer, so ligand pose has been confounded by the overall symmetry of the molecule. With cryo-EM we were able to isolate a fully-asymmetric ligand pose, all this in a 55kDa protein!

We think these states explain some odd ligand-binding behaviors of TTR, and open a window to the beginning of the process of amyloid formation.

The conformational landscape of human transthyretin revealed by cryo-EM bioRxiv - the preprint server for biology, operated by Cold Spring Harbor Laboratory, a research and educational institution

I'm happy to share the publication of my postdoctoral work from the Lander lab at Scripps. We solved previously-unobserved conformations of human TTR, an 55kDa amyloid-forming protein, to great resolution.
www.biorxiv.org/content/10.1...

baradlab.com (aka tomo.science ) is now online! Beginning to feel like a real lab!

Photo of my office with my nameplate on the wall

The Barad lab is open!

Unusual repetitive DNA sequence in the E. coli genome --> CRISPR ---> genome editing

Ψ Pseudouridine ---> mRNA immunogenicity and potency ---> mRNA COVID vaccine

#basicresearch

Dear funders, dear governments

please increase the basic research budget !