Kusal Samarasinghe
@kusals.bsky.social
Reposted by Kusal Samarasinghe
For our latest paper, we worked with SYROS Pharmaceuticals, the groups of Dylan Taatjes and Robin Dowell at CU Boulder, and @abhaykot.bsky.social. Junjie Feng in my lab determined the #cryoEM structure of the CDK7 inhibitor SY5609 bound to its target...
www.science.org/doi/10.1126/...
www.science.org/doi/10.1126/...
TFIIH kinase CDK7 drives cell proliferation through a common core transcription factor network
CDK7 kinase activity is found to control RNAPII transcription through a cohort of TFs that drive cell cycle and proliferation.
www.science.org
February 28, 2025 at 9:40 PM
For our latest paper, we worked with SYROS Pharmaceuticals, the groups of Dylan Taatjes and Robin Dowell at CU Boulder, and @abhaykot.bsky.social. Junjie Feng in my lab determined the #cryoEM structure of the CDK7 inhibitor SY5609 bound to its target...
www.science.org/doi/10.1126/...
www.science.org/doi/10.1126/...
An allosteric cyclin E-CDK2 site mapped by paralog hopping with covalent probes
www.nature.com/articles/s41...
www.nature.com/articles/s41...
An allosteric cyclin E-CDK2 site mapped by paralog hopping with covalent probes - Nature Chemical Biology
Development of a paralog-hopping approach leveraging chemical proteomic data on covalently liganded cysteines revealed an allosteric pocket shared by cysteine-containing and cysteine-less paralogous c...
www.nature.com
March 1, 2025 at 10:08 PM
An allosteric cyclin E-CDK2 site mapped by paralog hopping with covalent probes
www.nature.com/articles/s41...
www.nature.com/articles/s41...
Reposted by Kusal Samarasinghe
Excited about programming biology via induced proximity? Then mark June 2026 in your calendar and consider participating in the GRC Conference on Induced Proximity Modalities and Therapeutics that I am co-organizing with @danetteldaniels.bsky.social
tinyurl.com/brtuffam
tinyurl.com/brtuffam
January 30, 2025 at 7:32 PM
Excited about programming biology via induced proximity? Then mark June 2026 in your calendar and consider participating in the GRC Conference on Induced Proximity Modalities and Therapeutics that I am co-organizing with @danetteldaniels.bsky.social
tinyurl.com/brtuffam
tinyurl.com/brtuffam
Reposted by Kusal Samarasinghe
Exosome-based targeted delivery of NF-κB ameliorates age-related neuroinflammation in the aged mouse brain
www.nature.com/articles/s12...
www.nature.com/articles/s12...
Exosome-based targeted delivery of NF-κB ameliorates age-related neuroinflammation in the aged mouse brain - Experimental & Molecular Medicine
As we age, our bodies undergo changes that can lead to diseases like Alzheimer’s and Parkinson’s. A key factor in this process is inflammation in the brain, driven by a protein called NF-κB. Researche...
www.nature.com
January 29, 2025 at 2:29 AM
Exosome-based targeted delivery of NF-κB ameliorates age-related neuroinflammation in the aged mouse brain
www.nature.com/articles/s12...
www.nature.com/articles/s12...
Reposted by Kusal Samarasinghe
Our latest story: a protein-protein interaction between an E3 ubiquitin ligase and an autophagy adaptor affects liquid-liquid phase separation and sequestration of a key mediator of antioxidant signaling — but not via ubiquitination! Bravo to Lin Luan and Xiaofu Cao!
doi.org/10.1101/2025...
doi.org/10.1101/2025...
January 24, 2025 at 10:00 PM
Our latest story: a protein-protein interaction between an E3 ubiquitin ligase and an autophagy adaptor affects liquid-liquid phase separation and sequestration of a key mediator of antioxidant signaling — but not via ubiquitination! Bravo to Lin Luan and Xiaofu Cao!
doi.org/10.1101/2025...
doi.org/10.1101/2025...
Reposted by Kusal Samarasinghe
Our paper on computational design of chemically induced protein interactions is out in @natureportfolio.bsky.social. Big thanks to all co-authors, especially Anthony Marchand, Stephen Buckley and Bruno Correia!
t.co/vtYlhi8aQm
t.co/vtYlhi8aQm
January 15, 2025 at 4:37 PM
Our paper on computational design of chemically induced protein interactions is out in @natureportfolio.bsky.social. Big thanks to all co-authors, especially Anthony Marchand, Stephen Buckley and Bruno Correia!
t.co/vtYlhi8aQm
t.co/vtYlhi8aQm
Reposted by Kusal Samarasinghe
New to #ubiquitin? Been with it for a while? Either way this review may be for you 🤩
Excited to share our review article in @molcell.bsky.social, diving deep into everything #ubiquitin
Read here 👉: kwnsfk27.r.eu-west-1.awstrack.me/L0/https:%2F...
@cellpress.bsky.social
@wehi-research.bsky.social
Excited to share our review article in @molcell.bsky.social, diving deep into everything #ubiquitin
Read here 👉: kwnsfk27.r.eu-west-1.awstrack.me/L0/https:%2F...
@cellpress.bsky.social
@wehi-research.bsky.social
January 17, 2025 at 2:19 AM
New to #ubiquitin? Been with it for a while? Either way this review may be for you 🤩
Excited to share our review article in @molcell.bsky.social, diving deep into everything #ubiquitin
Read here 👉: kwnsfk27.r.eu-west-1.awstrack.me/L0/https:%2F...
@cellpress.bsky.social
@wehi-research.bsky.social
Excited to share our review article in @molcell.bsky.social, diving deep into everything #ubiquitin
Read here 👉: kwnsfk27.r.eu-west-1.awstrack.me/L0/https:%2F...
@cellpress.bsky.social
@wehi-research.bsky.social
Reposted by Kusal Samarasinghe
Protein production for cryoEM structure determination just got a lot cheaper - high resolution structure from half a plate of HEK cells with the "MIcro ISolation (MISO)" microfluidics-based approach. Congrats to the Brunner and Efremov labs in Brussels! www.biorxiv.org/content/10.1...
January 16, 2025 at 10:57 PM
Protein production for cryoEM structure determination just got a lot cheaper - high resolution structure from half a plate of HEK cells with the "MIcro ISolation (MISO)" microfluidics-based approach. Congrats to the Brunner and Efremov labs in Brussels! www.biorxiv.org/content/10.1...
Reposted by Kusal Samarasinghe
In the early 2000s, Don Hunt's lab at UVa started developing mass spec based approaches to characterize histone PTMs. I and others were fortunate to be at the right place at the right time back then. Read an account about those early days here.
www.mcponline.org/article/S153...
www.mcponline.org/article/S153...
On the Hunt for the Histone Code
In BriefIn the early 2000s before high resolution mass spectrometers were readily available, the Hunt lab developed many approaches to analyze histone modifications on low resolution instruments.
www.mcponline.org
December 12, 2024 at 2:30 PM
In the early 2000s, Don Hunt's lab at UVa started developing mass spec based approaches to characterize histone PTMs. I and others were fortunate to be at the right place at the right time back then. Read an account about those early days here.
www.mcponline.org/article/S153...
www.mcponline.org/article/S153...
PAGER: Alerts intracellular circuits about therapeutically relevant diverse primary messengers.
www.nature.com/articles/s41...
www.nature.com/articles/s41...
Synthetic GPCRs for programmable sensing and control of cell behaviour - Nature
Modular synthetic G-protein-coupled receptors with nanobody-based ligand-recognition domains can be designed and used to programme transgene expression, real-time fluorescence or endogenous G-protein ...
www.nature.com
December 4, 2024 at 6:10 PM
PAGER: Alerts intracellular circuits about therapeutically relevant diverse primary messengers.
www.nature.com/articles/s41...
www.nature.com/articles/s41...
Reposted by Kusal Samarasinghe
One amazing aspect of cryo-EM revolution is there are a bunch of giant E3 Ubiquitin ligase complexes that are mechanistically accessible- this seems cool from the Rapé lab
The molecular basis of integrated stress response silencing https://www.biorxiv.org/content/10.1101/2024.12.02.626349v1
The molecular basis of integrated stress response silencing https://www.biorxiv.org/content/10.1101/2024.12.02.626349v1
Chronic stress response activation impairs cell survival and causes devastating degenerative disease
www.biorxiv.org
December 3, 2024 at 4:28 AM
One amazing aspect of cryo-EM revolution is there are a bunch of giant E3 Ubiquitin ligase complexes that are mechanistically accessible- this seems cool from the Rapé lab
Reposted by Kusal Samarasinghe
Cool new work from Jenn Prescher and coworkers @ucirvine.bsky.social, “RNA lantern” technology for bioluminescence imaging of RNA transcripts
www.nature.com/articles/s41...
www.nature.com/articles/s41...
A modular platform for bioluminescent RNA tracking - Nature Communications
Studying RNA dynamics in vivo often relies on fluorogenic approaches, but these can be hampered by factors such as limited sensitivity and sample autofluorescence. Here, the authors describe an ultras...
www.nature.com
December 3, 2024 at 12:31 AM
Cool new work from Jenn Prescher and coworkers @ucirvine.bsky.social, “RNA lantern” technology for bioluminescence imaging of RNA transcripts
www.nature.com/articles/s41...
www.nature.com/articles/s41...
Targeting RNA-protein interactions with small molecules: promise and therapeutic potential
link.springer.com/article/10.1...
link.springer.com/article/10.1...
Targeting RNA-protein interactions with small molecules: promise and therapeutic potential - Medicinal Chemistry Research
The therapeutic potential of targeting protein-RNA interactions has not been fully explored. While several approaches to block the interactions between various RNA and protein partners have been devel...
link.springer.com
December 2, 2024 at 3:26 AM
Targeting RNA-protein interactions with small molecules: promise and therapeutic potential
link.springer.com/article/10.1...
link.springer.com/article/10.1...
Reposted by Kusal Samarasinghe
Written by Craig Lindsley:
pubs.acs.org/doi/10.1021/...
pubs.acs.org/doi/10.1021/...
Medicinal Chemistry Education and Training
OR SEARCH CITATIONS
pubs.acs.org
November 30, 2024 at 6:02 PM
Written by Craig Lindsley:
pubs.acs.org/doi/10.1021/...
pubs.acs.org/doi/10.1021/...
Very nice overview of the PROTAC concept and its applications:
www.cas.org/resources/ca...
www.cas.org/resources/ca...
PROTACs are revolutionizing small molecule drug development
PROTACs are driving small molecule drug development to treat cancer, neurodegenerative diseases and more
www.cas.org
November 30, 2024 at 5:52 PM
Very nice overview of the PROTAC concept and its applications:
www.cas.org/resources/ca...
www.cas.org/resources/ca...
Reposted by Kusal Samarasinghe
Allosteric activation of the SPRTN protease by ubiquitin maintains genome stability https://www.biorxiv.org/content/10.1101/2024.11.26.625192v1
Allosteric activation of the SPRTN protease by ubiquitin maintains genome stability https://www.biorxiv.org/content/10.1101/2024.11.26.625192v1
The DNA-dependent protease SPRTN maintains genome stability by degrading toxic DNA-protein crosslink
www.biorxiv.org
November 28, 2024 at 4:45 PM
Allosteric activation of the SPRTN protease by ubiquitin maintains genome stability https://www.biorxiv.org/content/10.1101/2024.11.26.625192v1