The three phases of my PhD thesis writing. Every. single. microsecond! (Pics from Pinterest, feelings mine)
Aanchal Mishra
@origichals.bsky.social
Human | Learner | PhD researcher studying SUMOylation (SUMO:SIM interactions) using Biochemistry and Structural Biology approach @msuskiewicz.bsky.social lab @cnrs.fr
Structural n biochemical POV: steric zipper; coiled coil; RING finger; hydrophobic collapse; domain swapping; disulfide scrambling; radical SAM; nucleophilic attack; IDR; peroxidation; amyloid fibril; glyoxylate shunt... I can go on n on..... Caroline truly gave an interesting exercise 👏
Ok what is the most death metal biology term? Cytokine storm? Programmed death 1? Executioner caspase? Other?
Serendipity always had a special place in Science and this paper is an example. ZBTB as a class of substrates of SUMO system, a system which is heavily populated by RanGAP1, PCNA etc, is both novel and visionary. ZBTB has a lot more to offer to the PTM world.
Happy to share our preprint on a subset of ZBTB BTB domains as highly efficient natural SUMO 'supersubstrates'. The work was spearheaded by a great postdoc, El Hadji Cisse, with input from other team members and in collaboration with @defossezlab.bsky.social and @ucagne.bsky.social
El-Hadji is a gem of a person and a great scientist. One won't regret having a person with rare combo of kindness and scientific brilliance.
The manuscript is currently in revision and we thank Editor and Reviewers for their input -- the paper will further improve! El Hadji, who is great and has a rare combination of chemistry and biochemistry skiils, has more almost-finished projects up his sleave and is looking for jobs/fellowships!
ColabFold 1.6.3 is out! 2.5x faster, pip-installable, ipSAE+pDockQ2 scores. Thanks Choonghwan Lee, Marielle Russo, Gyuri Kim 🐍pip install colabfold[alphafold] CF2 Sneak Peak with AF3/Boltz/Protenix/ESMFold2… 🐍pip install "colabfold[alphafold3]@git+https://github.com/sokrypton/ColabFold@af3-preview"
I’m genuinely confused about what PhD thesis writing even is at this point. Every time I start writin, I end up questioning my topic, my choices, my life, and my entire ability to form a coherent sentence. How many “hence, may, could” I’m supposed to sprinkle in b4 it qualifies as academic writing?
Stay tuned for this upcoming review- where transcription factors take filamentation to a whole new level, the molecular plot thickens and things get delightfully tangled. A lot more molecular intrigue coming your way soon.
We are currently writing a review ourselves - on various filament-forming transcription factors, so it was nice to brush up on FOXP3 and AIRE through this review.
Check out our new article if you are interested in disorder-mediated protein interactions, AlphaFold-based structural modeling and variant characterization: Https://rdcu.be/fw2oz Dx.doi.org/10.1038/s41594-026-01846-z
Variant characterization in the intrinsically disordered human proteome - Nature Structural & Molecular Biology
Proteome-wide prediction and structural modeling of disordered protein interaction interfaces advance characterization of disease-associated variants in disordered protein regions.
dx.doi.org
Excited to share our preprint introducing ASHI: the Atlas of SLiM-mediated Human protein-protein Interactions. By screening 800+ domains against the human intrinsically disordered regions, we map 20,000 SLiM-mediated interactions. Many thanks to everyone involved! www.biorxiv.org/content/10.6...
An Atlas of Short Linear Motif-Mediated Human Protein-Protein Interactions
Short linear motifs (SLiMs) within intrinsically disordered protein regions mediate transient interactions crucial for cell physiology. However, the global interaction landscape of human SLiMs remains...
biorxiv.org
Complexity does not begin when prediction becomes impossible. It begins when following everything is no longer the right way to predict! A brief overview in #ComplexityThoughts of the Dirac Medal 2026 and statistical physics of complex systems. open.substack.com/pub/manlius/...
When statistical physics escaped matter
The 2026 Dirac Medal celebrates Derrida, Dhar, Mézard and Sompolinsky, and a way of doing physics travelling far beyond its original domain
open.substack.com
De novo designed oligomers that respond to copper, small molecules, and phosphorylation... Using a single design strategy? 🧬⚙️ 🎉 Excited to share our new bioRxiv preprint—a collaboration between the Khmelinskaia, Correia, Schoeder and a Tinnefeld labs! www.biorxiv.org/content/10.6...
A generalizable interface-seeded framework for de novo design of functional oligomers
Protein oligomers are ubiquitous in biological systems and essential for function. However, the de novo design of oligomers that controllably assemble in response to exogenous stimuli remains challeng...
biorxiv.org
Our PhD Aanchal Mishra @origichals.bsky.social will defend this December. We'll be sad to see her go - she's been heart & soul of the team in many ways. Soon a highly recomm. *postdoc candidate* with good skills in protein biochem., crystal growth, ITC, advanced AlphaFold, passionate about science.
This is what accessible science looks like: lowering barriers, sharing knowledge, and enabling more people to participate in discovery.
New Experimental Google Colab Notebook now integrates AlphaFold3 with OpenFold3 and py2Dmol: colab.research.google.com/github/sokry... (1/3)
Crystallography’s first law: crystal beauty is inversely proportional to structural insight. Sad to see no diffraction of these crystals. P.S. First encounter with Eppendorf-shaped crystals. Natural selection has apparently been replaced by lab selection 😄
'If a control experiment fails, does that mean that the entire experiment is poorly designed and you must restart from scratch? Often, yes— but not always. I present five examples where failed control experiments triggered entirely new fields of research.' link.springer.com/article/10.1...
The controls that got out of control - EMBO Reports
EMBO Reports - When experimental controls go wrong, it does not necessarily mean your experiment is flawed. It might well be the first sign of something unexpected.
link.springer.com
Experimental ingenuity: The peak performance of our collective scientific brain cells under pressure- a highly sophisticated, temporarily engineered solution to prevent our 0.5 mL tubes from launching themselves off the rotator. Special thanks to panic n the last surviving fragment of creativity🤣🤣
You know the most destructive molecule for my experiments is Air? ITC thermogram shifts? Bubble. Gel refuses to run properly? Bubble. Crystallization ruined? Bubble. Mysterious signal artifacts? Also bubble. My troubleshooting career = fighting microscopic air pockets with a pipette tip. #origichals
Academia has many shades; today I’m thinking about one we don’t talk about enough: the life of a PI (coming from the perspective of a PhD student). It’s easy to assume that PhD/PostDocs do the heavy lifting of an entire project. But the reality is far more layered.
Days like these... Protein: expressed Transformation: done Cells: alive, thriving, judging Preculture: done Culture: done Pellet: secured like a tiny biological treasure Next day Lysis: done HisTrap: run… but, no protein!!! Gel: shows protein in the soluble extract Where's the protein, then?
To cleave or not to - especially for de-novo ones!?
Refined after adding the histidines, from both monomers of the assymetric unit. Very similar coordination spheres. If anyone is interested the tag is : GSGSHHWGSTHHHHHH. Dont ask me why it was designed that way 🙃 Im pretty sure the W is there to ensure absorbance at 280 nm
Why do intrinsically disordered proteins appear larger than they are in SDS-PAGE? We investigate how sequence properties affect SDS-PAGE mobility using synthetic IDRs. Conclusion: We need to consider both SDS binding and the compaction of protein-SDS complexes. www.biorxiv.org/content/10.6...
Our deepest fear is not that we are inadequate. Our deepest fear is that we are powerful beyond measure. It is our light, not our darkness that most frightens us. We ask ourselves, 'Who am I to be brilliant, gorgeous, talented, fabulous?' Actually, who are you not to be?
One of us is absolutely obsessed with capybaras. Another can’t stop talking about dachshunds. One lives and breathes anime. Another is powered entirely by romance novels. One expresses personality through funky socks. Another could survive on potatoes alone.
A gentle, fun reminder that science isn’t just about answers, but about the long, curious wandering that gets you there. Prof. Kleanthous shares his lab’s journey with warmth, making bacteriocins feel like companions along the way rather than just subjects of study.
A gift of an article from the inimitable Colin Kleanthous as he says a moving farewell to his laboratory. A brave, unrepentant and scientifically brilliant journey is described - please have a read, friends. www.jbc.org/article/S002...
How does molecular valency shape condensate assembly and function? We used the CO2-fixing organelle in algae—the pyrenoid—to find out… 🧵 Preprint here!: www.biorxiv.org/content/10.6... @cellarchlab.com @phaips.vd.st @biologyatyork.bsky.social #Rubisco #PhaseSeparation #Condensates #Pyrenoid
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I updated ipSAE code to handle Boltz2 files properly -- non-standard chainIDs/order, PDB input as well as mmCIF; other pull requests. github.com/DunbrackLab/.... Also updated preprint--fixed Latin grammar error in title - very embarrassing and added new figure. www.biorxiv.org/content/10.1...
pip install ipsae from www.linkedin.com/in/ullah-sam... www.youtube.com/watch?v=A5ph... PyPI pypi.org/project/ipsae/ His github fork github.com/ullahsamee/I... My github github.com/DunbrackLab/... Paper www.biorxiv.org/content/10.1... For designed protein binders www.biorxiv.org/content/10.1...
There are moments in life when certain people nearby just show up for you- no fanfare, no fuss, just pure goodness. And honestly? These people deserve a standing ovation, confetti cannons, and maybe even a parade.