Shikha Singh
@shikhas4858.bsky.social
Scientist BRIC-THSTI, India, former post-doc Columbia University, NY, structural biology, cryo-EM, Small-angle Xray scattering, ATPases, bioenergetics
Reposted by Shikha Singh
How does the well tolerated anti-hyperglycemic drug #metformin inhibit mitochondrial complex I?
In our new paper, we use structures, MD and kinetics to show that metformin inhibits by a distinct mechanism that more hydrophobic, less well tolerated, biguanides.
www.nature.com/articles/s41...
In our new paper, we use structures, MD and kinetics to show that metformin inhibits by a distinct mechanism that more hydrophobic, less well tolerated, biguanides.
www.nature.com/articles/s41...
Hydrophilic metformin and hydrophobic biguanides inhibit mitochondrial complex I by distinct mechanisms - Nature Structural & Molecular Biology
He, Teng and Yang et al. report how metformin, the widely used antidiabetic drug, inhibit its target, the respiratory complex I, through a distinct state-dependent, inhibitor trapping mechanism, thus ...
www.nature.com
November 10, 2025 at 6:35 PM
How does the well tolerated anti-hyperglycemic drug #metformin inhibit mitochondrial complex I?
In our new paper, we use structures, MD and kinetics to show that metformin inhibits by a distinct mechanism that more hydrophobic, less well tolerated, biguanides.
www.nature.com/articles/s41...
In our new paper, we use structures, MD and kinetics to show that metformin inhibits by a distinct mechanism that more hydrophobic, less well tolerated, biguanides.
www.nature.com/articles/s41...
Reposted by Shikha Singh
We have a preprint of a book chapter for you: Structural Analysis of Membrane Proteins in Cell-Derived Microvesicles.
We describe how to image membrane proteins in mid-sized vesicles using cryo-electron tomography
zenodo.org/records/1717...
We describe how to image membrane proteins in mid-sized vesicles using cryo-electron tomography
zenodo.org/records/1717...
Structural Analysis of Membrane Proteins in Cell-Derived Microvesicles
zenodo.org
September 22, 2025 at 12:36 PM
We have a preprint of a book chapter for you: Structural Analysis of Membrane Proteins in Cell-Derived Microvesicles.
We describe how to image membrane proteins in mid-sized vesicles using cryo-electron tomography
zenodo.org/records/1717...
We describe how to image membrane proteins in mid-sized vesicles using cryo-electron tomography
zenodo.org/records/1717...
Reposted by Shikha Singh
Thrilled that our work is now finally out in Nature Comms!
rdcu.be/eG3vP
We reveal cryo-EM structures of the MRN complex bound to DNA & TRF2 - showing how DNA breaks are sensed and regulated at telomeres.
Fantastic work by first authors @yilanfan.bsky.social @filizkuybu.bsky.social & Hengjun!
rdcu.be/eG3vP
We reveal cryo-EM structures of the MRN complex bound to DNA & TRF2 - showing how DNA breaks are sensed and regulated at telomeres.
Fantastic work by first authors @yilanfan.bsky.social @filizkuybu.bsky.social & Hengjun!
September 18, 2025 at 4:09 PM
Thrilled that our work is now finally out in Nature Comms!
rdcu.be/eG3vP
We reveal cryo-EM structures of the MRN complex bound to DNA & TRF2 - showing how DNA breaks are sensed and regulated at telomeres.
Fantastic work by first authors @yilanfan.bsky.social @filizkuybu.bsky.social & Hengjun!
rdcu.be/eG3vP
We reveal cryo-EM structures of the MRN complex bound to DNA & TRF2 - showing how DNA breaks are sensed and regulated at telomeres.
Fantastic work by first authors @yilanfan.bsky.social @filizkuybu.bsky.social & Hengjun!
Reposted by Shikha Singh
We finally wrote up the paper for LocScale-2.0.
edu.nl/pvhxv
Please try it out. LocScale is evolving & we are actively building in new features and improvements. Your feedback will help us shape the next steps.
Code: cryotud.github.io/locscale/
Work by @alok-bharadwaj.bsky.social and Reinier.
edu.nl/pvhxv
Please try it out. LocScale is evolving & we are actively building in new features and improvements. Your feedback will help us shape the next steps.
Code: cryotud.github.io/locscale/
Work by @alok-bharadwaj.bsky.social and Reinier.
We are happy to release LocScale2.0: a tool for context-aware, confidence-weighted cryoEM map optimisation.
Taking two half maps as input, LcoScale-2.0 produces feature-enhanced maps along with a robust confidence score that guides objective map interpretation.
cryotud.github.io/locscale/
Taking two half maps as input, LcoScale-2.0 produces feature-enhanced maps along with a robust confidence score that guides objective map interpretation.
cryotud.github.io/locscale/
September 15, 2025 at 7:39 AM
We finally wrote up the paper for LocScale-2.0.
edu.nl/pvhxv
Please try it out. LocScale is evolving & we are actively building in new features and improvements. Your feedback will help us shape the next steps.
Code: cryotud.github.io/locscale/
Work by @alok-bharadwaj.bsky.social and Reinier.
edu.nl/pvhxv
Please try it out. LocScale is evolving & we are actively building in new features and improvements. Your feedback will help us shape the next steps.
Code: cryotud.github.io/locscale/
Work by @alok-bharadwaj.bsky.social and Reinier.
Reposted by Shikha Singh
We are hiring at all levels, so please help spread the word! #RNAsky #ribosomes #signaling #translation sinha.biochem.utah.edu/join
Join — The Sinha Lab
We welcome curiosity-driven individuals excited to make foundational discoveries aimed at understanding and combating defects in translational control and proteostasis in a dynamic, collaborative, and...
sinha.biochem.utah.edu
August 21, 2025 at 7:09 PM
We are hiring at all levels, so please help spread the word! #RNAsky #ribosomes #signaling #translation sinha.biochem.utah.edu/join
Reposted by Shikha Singh
Latest from the lab! Analysis of everyone’s favorite regulatory mechanism in bacteria — the RF2 programmed frameshift! Likely present in the ancestor of bacteria, use of this mechanism is influenced by stop codon usage! Big congrats to @cassidyprints.bsky.social
journals.asm.org/doi/10.1128/...
journals.asm.org/doi/10.1128/...
Conservation and evolution of the programmed ribosomal frameshift in prfB across the bacterial domain | mBio
Translation termination is catalyzed by one of two release factors in bacteria, RF1 or RF2. It has been known for decades that RF2 levels in Escherichia coli are regulated by a programmed ribosomal frameshift within the prfB gene that encodes RF2. We ...
journals.asm.org
August 19, 2025 at 7:44 PM
Latest from the lab! Analysis of everyone’s favorite regulatory mechanism in bacteria — the RF2 programmed frameshift! Likely present in the ancestor of bacteria, use of this mechanism is influenced by stop codon usage! Big congrats to @cassidyprints.bsky.social
journals.asm.org/doi/10.1128/...
journals.asm.org/doi/10.1128/...
Reposted by Shikha Singh
Our #CryoET story on how a top antimalarial drug candidate perturbs the native malarial translation machinery is out @natsmb.nature.com🥳 rdcu.be/eBbrH
A massive team effort led by @leonieanton.bsky.social Meseret Haile & Wenjing Cheng in collaboration with Jerzy Dziekan & the Alan Cowman! #TeamTomo
A massive team effort led by @leonieanton.bsky.social Meseret Haile & Wenjing Cheng in collaboration with Jerzy Dziekan & the Alan Cowman! #TeamTomo
Integrated structural biology of the native malarial translation machinery and its inhibition by an antimalarial drug
Nature Structural & Molecular Biology - Integrated structural biology approach leveraging in situ cryo-electron tomography reveals molecular details of the native malarial translation...
rdcu.be
August 18, 2025 at 12:13 PM
Our #CryoET story on how a top antimalarial drug candidate perturbs the native malarial translation machinery is out @natsmb.nature.com🥳 rdcu.be/eBbrH
A massive team effort led by @leonieanton.bsky.social Meseret Haile & Wenjing Cheng in collaboration with Jerzy Dziekan & the Alan Cowman! #TeamTomo
A massive team effort led by @leonieanton.bsky.social Meseret Haile & Wenjing Cheng in collaboration with Jerzy Dziekan & the Alan Cowman! #TeamTomo
Reposted by Shikha Singh
Your sleep pressure is powered by your mitochondria! Sleep, energy, and ageing are all connected through mitochondrial bioenergetics in neurons. Brilliant work from Gero Miesenböck’s lab, just out in Nature @nature.com
www.nature.com/articles/s41...
www.nature.com/articles/s41...
July 16, 2025 at 10:57 PM
Your sleep pressure is powered by your mitochondria! Sleep, energy, and ageing are all connected through mitochondrial bioenergetics in neurons. Brilliant work from Gero Miesenböck’s lab, just out in Nature @nature.com
www.nature.com/articles/s41...
www.nature.com/articles/s41...
Reposted by Shikha Singh
Happy to share our latest work on the structure and assembly of holocentric kinetochores! Huge thanks to Ines for a very fruitful collaboration, Claudio for all the support, and congratulations to Christine and all co-authors!
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...
July 15, 2025 at 4:36 PM
Happy to share our latest work on the structure and assembly of holocentric kinetochores! Huge thanks to Ines for a very fruitful collaboration, Claudio for all the support, and congratulations to Christine and all co-authors!
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...
Reposted by Shikha Singh
Link here! guide.cryosparc.com/processing-d...
July 14, 2025 at 5:43 PM
Link here! guide.cryosparc.com/processing-d...
Reposted by Shikha Singh
Proud to share our work where we resolved a longstanding question regarding the existence of a human telomerase dimer and provided insights into its function. Led by 3 amazing lab members in collaboration with @yiliangding.bsky.social and @rdaslab.bsky.social.
www.science.org/doi/10.1126/...
www.science.org/doi/10.1126/...
Cryo-EM structure of human telomerase dimer reveals H/ACA RNP-mediated dimerization
Telomerase ribonucleoprotein (RNP) synthesizes telomeric repeats at chromosome ends using a telomerase reverse transcriptase (TERT) and a telomerase RNA (hTR in humans). Previous structural work showe...
www.science.org
July 10, 2025 at 9:26 PM
Proud to share our work where we resolved a longstanding question regarding the existence of a human telomerase dimer and provided insights into its function. Led by 3 amazing lab members in collaboration with @yiliangding.bsky.social and @rdaslab.bsky.social.
www.science.org/doi/10.1126/...
www.science.org/doi/10.1126/...
Reposted by Shikha Singh
A major KI initiative to recruit new assistant professors with outstanding proposals in all areas of medicine, biomedicine and public health. We offer an amazing research environment, great colleagues and generous startup packages. Check it out and get working on your applications! (repost please!)
Applications are now open! We are recruiting 20 Assistant Professors in a wide range of subject areas. We're looking for early-career researchers with strong scientific merits and future potential.
🔗 All positions: ki.se/en/about-ki/...
🔗 All positions: ki.se/en/about-ki/...
June 25, 2025 at 10:08 AM
A major KI initiative to recruit new assistant professors with outstanding proposals in all areas of medicine, biomedicine and public health. We offer an amazing research environment, great colleagues and generous startup packages. Check it out and get working on your applications! (repost please!)
Reposted by Shikha Singh
We have a 3-year funded postdoc position to work on structures of #amyloid filaments. If you are an expert in protein biochemistry, structural biology or #cryoEM / #cryoET, this could be for you! Feel free to email me with any questions. Come join us! 🤩
www.nature.com/naturecareer...
www.nature.com/naturecareer...
Postdoctoral Scientist - Structural Studies - Dr Sjors Scheres - LMB 2640 - Cambridgeshire job with MRC Laboratory of Molecular Biology (LMB) | 12840844
Postdoctoral Scientist Starting Salary: £41,344 Fixed term: 3 years MRC Laboratory of Molecular Biology, Cambridge, UK We are looking for a postdoc...
www.nature.com
June 25, 2025 at 2:01 PM
We have a 3-year funded postdoc position to work on structures of #amyloid filaments. If you are an expert in protein biochemistry, structural biology or #cryoEM / #cryoET, this could be for you! Feel free to email me with any questions. Come join us! 🤩
www.nature.com/naturecareer...
www.nature.com/naturecareer...
Reposted by Shikha Singh
We have a preprint for you
EHD2 forms rings on caveolae necks, in contrast to most EHDs forming helices. We determined its structure on membranes and show that N-term acts as a spacer
By Elena, Vasya @vasiliimikirtumov.bsky.social, Jeff &Oli Daumke www.biorxiv.org/content/10.1...
EHD2 forms rings on caveolae necks, in contrast to most EHDs forming helices. We determined its structure on membranes and show that N-term acts as a spacer
By Elena, Vasya @vasiliimikirtumov.bsky.social, Jeff &Oli Daumke www.biorxiv.org/content/10.1...
June 8, 2025 at 11:22 AM
We have a preprint for you
EHD2 forms rings on caveolae necks, in contrast to most EHDs forming helices. We determined its structure on membranes and show that N-term acts as a spacer
By Elena, Vasya @vasiliimikirtumov.bsky.social, Jeff &Oli Daumke www.biorxiv.org/content/10.1...
EHD2 forms rings on caveolae necks, in contrast to most EHDs forming helices. We determined its structure on membranes and show that N-term acts as a spacer
By Elena, Vasya @vasiliimikirtumov.bsky.social, Jeff &Oli Daumke www.biorxiv.org/content/10.1...
Reposted by Shikha Singh
Excited to share our new @science.org paper! Led by postdocs Ruchao Peng and Xin Xu, we used cryo-EM/ET to reveal the influenza ribonucleoprotein complex structure and its strand-sliding mechanism for RNA synthesis, paving the way for new antivirals.
www.science.org/doi/10.1126/...
www.science.org/doi/10.1126/...
Molecular basis of influenza ribonucleoprotein complex assembly and processive RNA synthesis
Influenza viruses replicate and transcribe their genome in the context of a conserved ribonucleoprotein (RNP) complex. By integrating cryo–electron microscopy single-particle analysis and cryo–electro...
www.science.org
May 15, 2025 at 7:51 PM
Excited to share our new @science.org paper! Led by postdocs Ruchao Peng and Xin Xu, we used cryo-EM/ET to reveal the influenza ribonucleoprotein complex structure and its strand-sliding mechanism for RNA synthesis, paving the way for new antivirals.
www.science.org/doi/10.1126/...
www.science.org/doi/10.1126/...
Reposted by Shikha Singh
Latest work from the lab - we identify a translation factor, YebC2, that reduces ribosome stalling in B. subtilis!
Congrats to co-first authors: grad students Hye-Rim Hong & Cassidy Prince & undergrad Dennis Wu @denniswu02.bsky.social
journals.plos.org/plosgenetics...
Congrats to co-first authors: grad students Hye-Rim Hong & Cassidy Prince & undergrad Dennis Wu @denniswu02.bsky.social
journals.plos.org/plosgenetics...
YebC2 resolves ribosome stalling and increases fitness of cells lacking EF-P and the ABCF ATPase YfmR
Author summary Polyproline motifs are essential structural features of many proteins but are difficult for the ribosome to synthesize. EF-P reduces ribosome pausing at polyproline motifs. Here, we sho...
journals.plos.org
April 13, 2025 at 3:11 PM
Latest work from the lab - we identify a translation factor, YebC2, that reduces ribosome stalling in B. subtilis!
Congrats to co-first authors: grad students Hye-Rim Hong & Cassidy Prince & undergrad Dennis Wu @denniswu02.bsky.social
journals.plos.org/plosgenetics...
Congrats to co-first authors: grad students Hye-Rim Hong & Cassidy Prince & undergrad Dennis Wu @denniswu02.bsky.social
journals.plos.org/plosgenetics...