John Schneekloth (Jay)
@jschneek.bsky.social
Chemical Biologist. Interested in RNA and DNA targeting, medicinal chemistry, and all things chemical biology. Follow my research here: http://bit.ly/4fpxjan
Honored to see that our collaborative work with Pratyush Tiwary and Adrian Ferré-D'Amaré on the ZTP riboswitch was selected as a very important paper by @angewandtechemie.bsky.social! onlinelibrary.wiley.com/doi/10.1002/...
Machine Learning‐Augmented Molecular Dynamics Simulations (MD) Reveal Insights Into the Disconnect Between Affinity and Activation of ZTP Riboswitch Ligands
This study combines computational and experimental approaches to study how natural and synthetic small molecules interact with the ZTP riboswitch, a bacterial RNA element that regulates gene expressi....
onlinelibrary.wiley.com
June 25, 2025 at 2:50 PM
Honored to see that our collaborative work with Pratyush Tiwary and Adrian Ferré-D'Amaré on the ZTP riboswitch was selected as a very important paper by @angewandtechemie.bsky.social! onlinelibrary.wiley.com/doi/10.1002/...
Hear-hear! Science making amazing progress and saving lives despite increasing barriers is something to be celebrated.
This piece by George Church in @statnews.com is the best response I've read, key quote (emphasis mine):
"Perhaps it's time to embrace the spirit of anti-complacency and pro-innovation WITHOUT HALLUCINATING A DEPRESSING DECLINE IN THE FACE OF REMARKABLE PROGRESS." 👏
www.statnews.com/2023/02/01/d...
"Perhaps it's time to embrace the spirit of anti-complacency and pro-innovation WITHOUT HALLUCINATING A DEPRESSING DECLINE IN THE FACE OF REMARKABLE PROGRESS." 👏
www.statnews.com/2023/02/01/d...
May 28, 2025 at 2:48 PM
Hear-hear! Science making amazing progress and saving lives despite increasing barriers is something to be celebrated.
Out now in @natchem.nature.com! Lots to unpack here, but in short - we show that SMM enabled fragment based design is useful on RNAs to improve chemical properties like affinity and brightness of fluorophore ligands.
www.nature.com/articles/s41...
www.nature.com/articles/s41...
Structure-informed design of an ultrabright RNA-activated fluorophore - Nature Chemistry
Fluorogenic RNA aptamers such as Mango are powerful tools for RNA imaging. An ultrabright RNA-activated fluorophore with improved photophysical performance has now been developed using a structure-inf...
www.nature.com
May 28, 2025 at 2:22 PM
Out now in @natchem.nature.com! Lots to unpack here, but in short - we show that SMM enabled fragment based design is useful on RNAs to improve chemical properties like affinity and brightness of fluorophore ligands.
www.nature.com/articles/s41...
www.nature.com/articles/s41...
New work from the lab - With Pratyush Tiwary and Adrian Ferre-D'Amare, we study ligands that activate the ZTP riboswitch. Experimental and theoretical approaches show that ligand on rates influence activity by non-obvious mechanisms when targeting RNA!
onlinelibrary.wiley.com/doi/10.1002/...
onlinelibrary.wiley.com/doi/10.1002/...
Machine learning‐augmented molecular dynamics simulations (MD) reveal insights into the disconnect between affinity and activation of ZTP riboswitch ligands
The challenge of targeting RNA with small molecules necessitates a better understanding of RNA-ligand interaction mechanisms. However, the dynamic nature of nucleic acids, their ligand-induced stabil...
onlinelibrary.wiley.com
May 8, 2025 at 6:44 PM
New work from the lab - With Pratyush Tiwary and Adrian Ferre-D'Amare, we study ligands that activate the ZTP riboswitch. Experimental and theoretical approaches show that ligand on rates influence activity by non-obvious mechanisms when targeting RNA!
onlinelibrary.wiley.com/doi/10.1002/...
onlinelibrary.wiley.com/doi/10.1002/...
Reposted by John Schneekloth (Jay)
Congratulations to Evan J. Burke, a grad student in the Krebs and Bollinger labs in Penn State's Department of Chemistry, on being named a 2025 #ACSBIOL Young Investigator!
@jmarbol21.bsky.social
@jmarbol21.bsky.social
May 6, 2025 at 12:01 PM
Congratulations to Evan J. Burke, a grad student in the Krebs and Bollinger labs in Penn State's Department of Chemistry, on being named a 2025 #ACSBIOL Young Investigator!
@jmarbol21.bsky.social
@jmarbol21.bsky.social
Another new piece of work from the lab - I played a small role in this really exciting work coming out of the Pearson lab at Sick Kids in Toronto dealing with preclinical studies on CAG repeat instability in Huntington disease. Check it out: www.biorxiv.org/content/10.1...
Interventionally targeting somatic CAG expansions can be a rapid disease-modifying therapeutic avenue: Preclinical evidence.
Huntington disease (HD) is caused by inherited CAG expansions, which continue expanding somatically in affected brain regions to hasten disease onset and progression. Therapeutically diminishing somat...
www.biorxiv.org
April 30, 2025 at 4:40 PM
Another new piece of work from the lab - I played a small role in this really exciting work coming out of the Pearson lab at Sick Kids in Toronto dealing with preclinical studies on CAG repeat instability in Huntington disease. Check it out: www.biorxiv.org/content/10.1...
Hey, check it out - new work from the lab! We report the design of design traceless, reversible small molecule photocrosslinking probes that can be used to photochemically control the translation of mRNAs just using molecular recognition! Congrats to all! onlinelibrary.wiley.com/doi/10.1002/...
Harnessing Molecular Recognition for Small‐Molecule‐Mediated Reversible Photochemical Control Over mRNA Translation
A small molecule ligand undergoes traceless, reversible photocrosslinking to PreQ1 RNA aptamer in a selective manner, dependent on both the RNA sequence/structure and ligand chemical structure. A cag...
onlinelibrary.wiley.com
April 25, 2025 at 5:30 PM
Hey, check it out - new work from the lab! We report the design of design traceless, reversible small molecule photocrosslinking probes that can be used to photochemically control the translation of mRNAs just using molecular recognition! Congrats to all! onlinelibrary.wiley.com/doi/10.1002/...
Reposted by John Schneekloth (Jay)
We're looking for 1-2 enthusiastic early career chemists to join our Open Chemistry team at @hhmijanelia.bsky.social. Come help us create amazing dyes and share them with the world. Please share with the best recent/soon-to-be B.S. chemists you know! bit.ly/42w8C6N
Research Technician - Open Chemistry
Primary Work Address: 19700 Helix Drive, Ashburn, VA, 20147 Current HHMI Employees, click here to apply via your Workday account. Summary: Open Chemistry is a collaborative research group whose missio...
bit.ly
April 11, 2025 at 7:27 PM
We're looking for 1-2 enthusiastic early career chemists to join our Open Chemistry team at @hhmijanelia.bsky.social. Come help us create amazing dyes and share them with the world. Please share with the best recent/soon-to-be B.S. chemists you know! bit.ly/42w8C6N
Reposted by John Schneekloth (Jay)
Great news: NIH postbac program is recruiting again! If your grad school plans were affected by program cutbacks or admissions freezes this year I highly encourage you to apply, this could be a perfect opportunity. Please repost.
www.training.nih.gov/research-tra...
www.training.nih.gov/research-tra...
www.training.nih.gov
April 10, 2025 at 1:22 AM
Great news: NIH postbac program is recruiting again! If your grad school plans were affected by program cutbacks or admissions freezes this year I highly encourage you to apply, this could be a perfect opportunity. Please repost.
www.training.nih.gov/research-tra...
www.training.nih.gov/research-tra...
New work from my awesome colleague @vidigaljoana.bsky.social!
What was that you said? You are looking for new #RNA research to read in the weekend?
You are in luck!
📣 📣 Check out the new preprint from our lab!!!! 📣 📣
www.biorxiv.org/content/10.1...
You are in luck!
📣 📣 Check out the new preprint from our lab!!!! 📣 📣
www.biorxiv.org/content/10.1...
AGO2 slicing of a domesticated retrotransposon is necessary for normal vasculature development
Argonaute (AGO) mediated slicing of RNA, also known as RNAi, is a highly conserved phenomenon that is evolutionarily linked to the repression of transposons and other repeats. Although RNAi is no long...
www.biorxiv.org
April 4, 2025 at 10:42 PM
New work from my awesome colleague @vidigaljoana.bsky.social!
Reposted by John Schneekloth (Jay)
The final #ACSBIOL sessions of #ACSSpring2025 are tomorrow morning, Thursday the 27th:
📰 Current Topics in #Biochem and #ChemBio, Room 31A
👩🎓 Undergraduate and Graduate Research, Hal G/H Room 8
Be sure to check out these excellent presentations!
📰 Current Topics in #Biochem and #ChemBio, Room 31A
👩🎓 Undergraduate and Graduate Research, Hal G/H Room 8
Be sure to check out these excellent presentations!
March 26, 2025 at 11:33 PM
The final #ACSBIOL sessions of #ACSSpring2025 are tomorrow morning, Thursday the 27th:
📰 Current Topics in #Biochem and #ChemBio, Room 31A
👩🎓 Undergraduate and Graduate Research, Hal G/H Room 8
Be sure to check out these excellent presentations!
📰 Current Topics in #Biochem and #ChemBio, Room 31A
👩🎓 Undergraduate and Graduate Research, Hal G/H Room 8
Be sure to check out these excellent presentations!
Reposted by John Schneekloth (Jay)
#ACSBIOL Sessions on Wednesday, 26th at #ACSSpring2025:
Morning, Room 31A:
🏆 Eli Lilly Award to @brianliau.bsky.social
Afternoon, Room 31A:
🏆 ACS Chemical Biology Young Investigator Award to @jeremybaskin.bsky.social
Evening, Hall B2/C:
📜 Poster Session, Current Topics
@pubs.acs.org
Morning, Room 31A:
🏆 Eli Lilly Award to @brianliau.bsky.social
Afternoon, Room 31A:
🏆 ACS Chemical Biology Young Investigator Award to @jeremybaskin.bsky.social
Evening, Hall B2/C:
📜 Poster Session, Current Topics
@pubs.acs.org
March 25, 2025 at 11:58 PM
#ACSBIOL Sessions on Wednesday, 26th at #ACSSpring2025:
Morning, Room 31A:
🏆 Eli Lilly Award to @brianliau.bsky.social
Afternoon, Room 31A:
🏆 ACS Chemical Biology Young Investigator Award to @jeremybaskin.bsky.social
Evening, Hall B2/C:
📜 Poster Session, Current Topics
@pubs.acs.org
Morning, Room 31A:
🏆 Eli Lilly Award to @brianliau.bsky.social
Afternoon, Room 31A:
🏆 ACS Chemical Biology Young Investigator Award to @jeremybaskin.bsky.social
Evening, Hall B2/C:
📜 Poster Session, Current Topics
@pubs.acs.org
Congrats @rche54.bsky.social, nice work!
Proud to share this work from my group in the intramural research program at NIH! We describe a new kind of conjugate made from a small molecule adenosine analog linked to a GPCR targeting nanobody to make antibody drug conjugates that potently and specifically activate signaling (1/n) 🧪 #chembio
Nanobody-based conjugates targeting small molecule-binding GPCRs and exhibiting logic-gated signaling https://www.biorxiv.org/content/10.1101/2025.03.07.642093v1
March 13, 2025 at 2:08 PM
Congrats @rche54.bsky.social, nice work!
Check out this awesome paper from my colleague @eunayoo.bsky.social about activity-based probes for USP18! www.nature.com/articles/s41...
Chemical tools to define and manipulate interferon-inducible Ubl protease USP18 - Nature Communications
USP18 is a multifunctional cysteine protease involved in IFN pathways. Here, the authors report chemical probes and chemoproteomics platforms that allow to detect and perturb USP18 activity in complex...
www.nature.com
January 22, 2025 at 9:36 PM
Check out this awesome paper from my colleague @eunayoo.bsky.social about activity-based probes for USP18! www.nature.com/articles/s41...
We often focus on publicizing our work to other scientists but it's just as important to have journalists communicate with non-scientists as well!
ALL journalists can benefit from the resources and best practices developed by the network of writers who have flourished in science journalism. Science writers and leaders like Siri and Laura help lift unheard voices and share knowledge of diligent reporting. 🧪https://www.theopennotebook.com/
December 19, 2024 at 4:12 PM
We often focus on publicizing our work to other scientists but it's just as important to have journalists communicate with non-scientists as well!
Reposted by John Schneekloth (Jay)
I am about to survive my 1047th week in medicinal chemistry. This editorial is a visit on memory lane. Yes, starting in MedChem initially looks very daunting. MedChems love abbreviations & specialist slang to scare off laymen. But overcoming these hurdles is so rewarding in many dimensions.
December 19, 2024 at 12:10 PM
I am about to survive my 1047th week in medicinal chemistry. This editorial is a visit on memory lane. Yes, starting in MedChem initially looks very daunting. MedChems love abbreviations & specialist slang to scare off laymen. But overcoming these hurdles is so rewarding in many dimensions.
What a week! Really proud to share this work with Venkat Gopalan and Damien Wilburn in Nucleic Acids Research. We show that our SMM platform can be used to identify allosteric chemical inhibitors of an archaeal RNase P, an ancient ribozyme. academic.oup.com/nar/advance-...
Use of a small molecule microarray screen to identify inhibitors of the catalytic RNA subunit of Methanobrevibacter smithii RNase P
Abstract. Despite interest in developing therapeutics that leverage binding pockets in structured RNAs—whose dysregulation leads to diseases—such drug disc
academic.oup.com
December 19, 2024 at 3:50 PM
What a week! Really proud to share this work with Venkat Gopalan and Damien Wilburn in Nucleic Acids Research. We show that our SMM platform can be used to identify allosteric chemical inhibitors of an archaeal RNase P, an ancient ribozyme. academic.oup.com/nar/advance-...
Thrilled to see our work in @pnas.org this week! With Pratyush Tiwary, we show that "thermodynamic maps" can be used to infer and predict information about RNA 3D structural ensembles! Proud to have played a small role in this exciting work. www.pnas.org/doi/10.1073/...
www.pnas.org
December 19, 2024 at 3:40 PM
Thrilled to see our work in @pnas.org this week! With Pratyush Tiwary, we show that "thermodynamic maps" can be used to infer and predict information about RNA 3D structural ensembles! Proud to have played a small role in this exciting work. www.pnas.org/doi/10.1073/...
This is deeply concerning!
🧪A disturbing trend.
The editor-in-chief of a high profile journal (IF=13.6) was recently offered the opportunity to make up to $250k/year to approve fake papers in his journal ($5k per paper). He declined & reported it. 👍
But, would other editors be tempted? 😬
richardtol.substack.com/p/crime-pays
The editor-in-chief of a high profile journal (IF=13.6) was recently offered the opportunity to make up to $250k/year to approve fake papers in his journal ($5k per paper). He declined & reported it. 👍
But, would other editors be tempted? 😬
richardtol.substack.com/p/crime-pays
Crime pays
A paper mill offered me $250,000 per year
richardtol.substack.com
December 19, 2024 at 3:10 PM
This is deeply concerning!
Reposted by John Schneekloth (Jay)
Americans are now one-third less likely to die from cancer at the same ages as Americans in 1990
December 9, 2024 at 4:36 PM
Americans are now one-third less likely to die from cancer at the same ages as Americans in 1990
Really excited to see this work out! In collaboration with Prof. Jen Prescher, we showed that their cyclopropenone labeling strategy can be applied to structured RNA! Thrilled to work with this fantastic team of scientists. pubs.acs.org/doi/10.1021/...
Bioorthogonal Cyclopropenones for Investigating RNA Structure
RNA sequences encode structures that impact protein production and other cellular processes. Misfolded RNAs can also potentiate disease, but a complete picture is lacking. To establish more comprehens...
pubs.acs.org
December 9, 2024 at 9:48 PM
Really excited to see this work out! In collaboration with Prof. Jen Prescher, we showed that their cyclopropenone labeling strategy can be applied to structured RNA! Thrilled to work with this fantastic team of scientists. pubs.acs.org/doi/10.1021/...
Reposted by John Schneekloth (Jay)
One of the reasons Bluesky is seeing more engagement: other platforms have adopted the behaviour of de-prioritising external links (like, say, to research papers) due to Ad models.
See this: bsky.app/profile/alt...
Here links can be freely shared without being drowned out or de-emphasized
See this: bsky.app/profile/alt...
Here links can be freely shared without being drowned out or de-emphasized
@altmetric.com on Bluesky
We’re no experts but this sounds like it might be suboptimal for disseminating research.
[contains quote post or other embedded content]
bsky.app
December 3, 2024 at 2:01 PM
One of the reasons Bluesky is seeing more engagement: other platforms have adopted the behaviour of de-prioritising external links (like, say, to research papers) due to Ad models.
See this: bsky.app/profile/alt...
Here links can be freely shared without being drowned out or de-emphasized
See this: bsky.app/profile/alt...
Here links can be freely shared without being drowned out or de-emphasized
Reposted by John Schneekloth (Jay)
🎉 Our grad student @katherinelegg.bsky.social is a co-author on a new preprint about the genetic requirements and nutrient needs for Staphylococcus aureus growth in cystic fibrosis sputum. Congrats to @gramnegativity.bsky.social and all involved! shorturl.at/yfZQA 🧬 #CysticFibrosis #Microbiology
Analysis of genetic requirements and nutrient availability for Staphylococcus aureus growth in cystic fibrosis sputum
Staphylococcus aureus is one of the most common pathogens isolated from the lungs of people with cystic fibrosis (CF), but little is known about its ability to colonize this niche. We performed a Tn-s...
pmc.ncbi.nlm.nih.gov
December 2, 2024 at 3:00 PM
🎉 Our grad student @katherinelegg.bsky.social is a co-author on a new preprint about the genetic requirements and nutrient needs for Staphylococcus aureus growth in cystic fibrosis sputum. Congrats to @gramnegativity.bsky.social and all involved! shorturl.at/yfZQA 🧬 #CysticFibrosis #Microbiology
Reposted by John Schneekloth (Jay)
Years after the idea and preliminary experiments, Claire Coupland's amazing structure of the endogenous vacuolar- or vesicular-ATPase in its NATIVE vesicle is now in bioRxiv "High resolution cryo-EM of V-ATPase in native synaptic vesicles"
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...
April 2, 2024 at 5:11 PM
Years after the idea and preliminary experiments, Claire Coupland's amazing structure of the endogenous vacuolar- or vesicular-ATPase in its NATIVE vesicle is now in bioRxiv "High resolution cryo-EM of V-ATPase in native synaptic vesicles"
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...
Reposted by John Schneekloth (Jay)
December 2, 2024 at 2:07 PM