In this seminar I will briefly review some success stories of Machine Learning in biology and speculate on what it will take to enable a much more substantial progress. I will specifically discuss connections between embryology and biology of aging - the field which remains perhaps the most promising and most fraudulent over thousands of years in history of the medical science. I will present my pharmaco-biology approaches  and suggest where theoretical approaches and modeling can make a big difference in a search for novel therapeutic interventions.   

More information on Dr. Peshkin's work:

Blueprint For Radically Open, Citizen Science Approach To Aging Research
https://www.bio-itworld.com/news/2022/03/23/blueprint-for-radically-open-citizen-science-approach-to-aging-research

A preprint on Reverse Engineering via poly-pharmacology of kinase inhibitors   https://www.biorxiv.org/content/10.1101/2020.09.26.312348

Join the Teams meeting : shorturl.at/bjT25

In this seminar I will briefly review some success stories of Machine Learning in biology and speculate on what it will take to enable a much more substantial progress. I will specifically discuss connections between embryology and biology of aging - the field which remains perhaps the most promising and most fraudulent over thousands of years in history of the medical science. I will present my pharmaco-biology approaches  and suggest where theoretical approaches and modeling can make a big difference in a search for novel therapeutic interventions.   

More information on Dr. Peshkin's work:

Blueprint For Radically Open, Citizen Science Approach To Aging Research
https://www.bio-itworld.com/news/2022/03/23/blueprint-for-radically-open-citizen-science-approach-to-aging-research

A preprint on Reverse Engineering via poly-pharmacology of kinase inhibitors   https://www.biorxiv.org/content/10.1101/2020.09.26.312348

Join the Teams meeting : shorturl.at/bjT25

In this seminar I will briefly review some success stories of Machine Learning in biology and speculate on what it will take to enable a much more substantial progress. I will specifically discuss connections between embryology and biology of aging - the field which remains perhaps the most promising and most fraudulent over thousands of years in history of the medical science. I will present my pharmaco-biology approaches  and suggest where theoretical approaches and modeling can make a big difference in a search for novel therapeutic interventions.   

More information on Dr. Peshkin's work:

Blueprint For Radically Open, Citizen Science Approach To Aging Research
https://www.bio-itworld.com/news/2022/03/23/blueprint-for-radically-open-citizen-science-approach-to-aging-research

A preprint on Reverse Engineering via poly-pharmacology of kinase inhibitors   https://www.biorxiv.org/content/10.1101/2020.09.26.312348

Join the Teams meeting : shorturl.at/bjT25

Single-cell transcriptomics and single-cell epigenomics allow building cell atlases of any tissue and species, providing new opportunities to predict gene regulatory networks that control the identity of cell types and cell states. I will present new computational strategies that take advantage of the joint analysis of scRNA-seq and scATAC-seq data, and that derive “enhancer-GRNs” (eGRN) with key transcription factors, genomic enhancers, and predicted target genes per cell type. On the scATAC-seq side, our strategy exploits topic modelling and motif discovery in co-accessible regions to predict TFs. On the scRNA-seq side, we use random forest regression (GENIE3) to link both accessible regions, as well as upstream TFs, to candidate target genes. In parallel, we use deep learning on the scATAC-seq topics to prioritize enhancers based on TF motif combinations. I will discuss the results of several case studies where we applied this strategy to, including the Drosophila brain, the mammalian brain, and the mouse liver. Finally, I will discuss how enhancer models based on deep learning can be exploited to design synthetic enhancers for Drosophila and human cell types.

The seminar will also be broadcasted live. Please click here.

How cells regulate the timing of cell division and the initiation of new rounds of DNA replication is a longstanding problem. In recent years, new models of cell size homeostasis have been proposed for bacteria, yeast and mammalian cells. A common method to test such models has been to compare the correlations predicted by them to those experimentally measured (e.g., the correlation of cell size at birth and division or the generation time). However, distinct models may predict identical sets of correlation coefficients. I will show that using conditional independence tests (considering the correlation of a pair of variables conditioned on a third) provides new insights into the problem. We find that for E. coli replication is tightly coupled to division in slow growth conditions while in fast growth conditions the division event is influenced by additional processes.

Le réseau transgolgi (TGN) est la station de tri centrale de la voie sécrétoire, où les protéines de cargaison sont emballées dans différents transporteurs pour être exportées vers leur destination respective. Malgré son importance fondamentale dans le maintien de l'homéostasie et de la fonction cellulaire, la façon dont les cargaisons sécrétoires sont triées et spécifiquement emballées dans des transporteurs naissants au niveau du TGN reste encore mal comprise. Dans cet exposé, je me concentrerai sur l'explication de nos résultats récents sur le tri des cargaisons dans une classe de transporteurs riches en sphingomyéline, Rab6 et dépendant de la protéine kinase D (PKD), nommés CARTS.  Je présenterai nos résultats montrant que la protéine transmembranaire (TM) de type I à passage unique TGN46 (une protéine contenue dans CARTS) joue un rôle clé dans le tri de ses clients dans les transporteurs naissants. Ces données révèlent que les déterminants topologiques qui décrivent la bonne localisation intracellulaire et intra-Golgi de TGN46, ainsi que sa propre incorporation dans le SRSAC, sont principalement contenus dans son domaine luminal. En particulier, je présenterai des preuves montrant que le domaine luminal de TGN46 est à la fois nécessaire et suffisant pour l'exportation des protéines de cargaison dans le STCC et que ce domaine est le médiateur de la fonction de tri des cargaisons de TGN46. Il est intéressant de noter que ce domaine forme des gouttelettes liquides in vitro par le biais d'une séparation de phase liquide-liquide, un mécanisme physique qui pourrait contribuer au tri des cargaisons médié par TGN46. Dans l'ensemble, nos données suggèrent un rôle essentiel pour TGN46 dans le tri des protéines de cargaison dans les transporteurs au niveau du TGN.

The interferon (IFN) response is a critical arm of the innate immune response and a major host defense mechanism against viral infections. Numerous genes that contribute to this antiviral state remain to be identified and characterized. Using large-scale loss-of-function strategies, we screened siRNAs or gRNAs libraries targeting hundreds of IFN-stimulated genes (ISGs) in IFN-treated cells infected with human RNA viruses, including coronaviruses and flaviviruses. We recovered previously unrecognized human genes able to modulate the replication these RNA viruses in an IFN-dependent manner. For instance, we identified DAXX, a scaffold protein residing in PML nuclear bodies, as a potent SARS-CoV-2 specific antiviral factor and MTA2, a chromatin remodeling protein, as a factor inhibiting flavivirus replication. We are also expanding our studies to the identification and characterization of ISGs in animal species that serve as viral reservoirs, such as bats. Finally, we are studying the mechanisms by which these viruses counteract the IFN response. For instance, through unbiased screening approaches, we recently uncovered a novel mechanism by which tick-borne flaviviruses antagonize IFN signaling. Our studies should open new perspectives to target weakness points in the life cycle of these emerging RNA viruses.

Join the Teams meeting : shorturl.at/euzFZ

Our research uses chemistry principles to address questions of importance in life sciences and molecular medicine. This lecture will cover recent examples of emerging areas in our group in:

* methods for site-selective chemical modification of proteins and antibodies;

* bioorthogonal cleavage reactions for targeted drug activation in cells;

* click-degraders, small molecules that when in proximity can degrade RNA, akin to       ribonucleases. Using click-degraders we developed 1) meCLICK-Seq, a powerful method for the study of diverse aspects of cellular RNA methylation, and 2) proximity-driven small molecule RNA degraders to target and degrade SARS-CoV-2 genomes and exert an antiviral effect in disease models.

Human cells encode 6 topoisomerases to regulate the topology of nucleic acids. While yeast has only one Top3, mammals encode two Type IA topoisomerases: topoisomerase III alpha (TOP3A) and topoisomerase III beta (TOP3B). We will review the importance of these two enzymes and present new insights on their biochemistry, molecular structure, and biological functions for replicating the nuclear and mitochondrial genomes (TOP3A) and for RNA metabolism and R-loop dissolution (TOP3B).

And online: Click here to join by Teams

Les interférons de type I (IFN) activent les programmes antimicrobiens intracellulaires et influencent le développement des réponses immunitaires innées et adaptatives. Nous discuterons de nos résultats en abordant la biologie des IFN dans le syndrome de Down (DS). Ce syndrome est la conséquence d'une anomalie chromosomique appelée " trisomie 21 " dans laquelle le chromosome 21 est partiellement ou totalement triplé. Les sous-unités qui composent le récepteur de l'IFN-I (IFNAR1 et IFNAR2), comme d'autres gènes importants pour l'immunologie, sont codés sur ce chromosome et leur expression est fortement augmentée. Cela génère une importante dysrégulation immunologique. Nous discuterons des caractéristiques du compartiment des cellules T, de la fonctionnalité des Tregs, et de l'impact de la signalisation IFN sur les différents sous-ensembles de cellules T, qui pourraient expliquer les différentes susceptibilités de cette population à développer certaines pathologies telles que les tumeurs solides et l'auto-immunité. D'autre part, la signalisation compétente de l'IFN de type I est à la base de la plupart des mécanismes immunitaires anti-tumoraux et s'est récemment avérée essentielle à l'efficacité de plusieurs agents anticancéreux et de l'immunothérapie.  Dans cet exposé, nous discuterons de nos récentes découvertes concernant le potentiel des agonistes TLR en tant qu'inducteurs de l'IFN de type I et, par conséquent, en tant que modulateurs puissants de la composition de l'infiltrat tumoral, capables de faire basculer l'environnement tumoral immunosuppressif vers une immunité anti-tumorale.