stephanhacker2.bsky.social
Assistant Professor at Leiden University. Covalent inhibitors and chemoproteomics for antibiotics. Views my own. he/him/his. https://orcid.org/0000-0001-5420-4824
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Thank you so much for visiting us, Andrea!
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Finally, she showcased the application of FlashCaps to control gene expression in living zebrafish with spatiotemporal resolution. (4/4) www.nature.com/articles/s42...
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Next, she talked about her group's development of FlashCaps, mRNA cap analogs that allow to control the translation of mRNAs with light. (3/4) onlinelibrary.wiley.com/doi/full/10....
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Initially, she talked about the use of a propargylated amino acid that gets incorporated into SAM and then further into RNA using methyl transferases. This allows them to study several different mRNA modifications in living cells. (2/4) www.nature.com/articles/s41...
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Finally, he talked about how his group uses clinical candidates for human kinases to screen for new antimalarial drugs. Interesting insights into the activity of the mTOR inhibitor Sapanisertib against malaria mainly by targeting PI4Kβ. (4/4) www.science.org/doi/10.1126/...
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He then talked about his group's focus on targeting Plasmodium lipid and protein kinases as promising targets against malaria. Important thoughts to think about likelihood of resistance development early in the drug discovery process. (3/4) pubs.acs.org/doi/10.1021/...
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He started by a clear explanation of the background of malaria and the life cycle of the underlying pathogens including P. falciparum. An important point was, that novel mechanisms of action and compounds that the pathogen has never seen before are needed to slow down resistance development. (2/4)
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Finally, she discussed how LiP-MS can yield information on enzyme activity changes, phosphorylation, protein aggregation and complex formation. In this way, it gives a lot of complementary information to expression proteomics for mechanistic hypothesis generation. (6/6) www.cell.com/cell/fulltex...
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Next, she talked about a method based on LiP-MS (FLiP–MS) that allows studying protein-protein interactions and their dynamics on a proteome-wide scale. Interesting potential to screen proximity inducers and protein complex destabilizers. (5/6) www.nature.com/articles/s41...
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She then talked about the use of LiP-MS to study the mechanism-of-action of osmolytes. Using LiP-MS in combination with a temperature gradient, they can study compound binding, (de)stabilization and aggregation with resolution of individual functional sites. (4/6) www.nature.com/articles/s41...
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She then talked about the use of LiP-MS to identify targets of protein ligands proteome-wide. Interesting insights into the ability of this method to map binding sites and understand, if the ligands introduce larger structural changes. (3/6) www.cell.com/trends/bioch...
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She started by introducing her group's work on establishing MS-based limited proteolysis methods (LiP-MS) to understand structural changes on a proteome-wide level at a depth of >4000 proteins. (2/6) www.nature.com/articles/s41...
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Interesting insights also into the exploration of pharmacogenomic effects to tailor treatment regimes in Africa for specifically relevant diseases such as malaria and tuberculosis. (3/3) www.medrxiv.org/content/10.1...
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Exciting applications to analysing and visualising chemoproteomic data of in cell target engagement of fully functionalized photoprobes in collaboration with @georgwinter.bsky.social. (2/3) www.science.org/doi/10.1126/...
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Finally, he talked about how additional criteria on top of biological activity, like PKPD properties and synthesizability, can be taken into account during the predictions. Interesting insights into the LED3 Score for synthesizability. (4/4) chemrxiv.org/engage/chemr...
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He then talked about the use of structural information from AlphaFold2 to predict binders to proteins, for which no known binders exist. (3/4) pubs.acs.org/doi/10.1021/...
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He started by talking about the challenge of encoding chemical information in a way that it can be used for AI models and then using this to predict activity on desired targets and off-targets. (2/4) jcheminf.biomedcentral.com/articles/10....