Lecture series Translational Bioinformatics and Systems Biomedicine "GETTING INSIGHTS INTO CELL BIOLOGY BY NETWORK RECONSTRUCTION AND MODELLING" - Prof Boris Kholodenko
18/10/2018 11:30 to 18/10/2018 12:30 (Europe/Luxembourg)
Speaker
Prof Boris Kholodenko is Professor of Systems Biology, Deputy Director of Systems Biology Ireland (SBI), Conway Institute Member, University College Dublin, Ireland Professor Adjunct of Pharmacology, Department of Pharmacology, Yale University School of Medicine, New Haven, USA.
Abstract
Omics technologies have generated large inventories of genes, transcripts, proteins, and metabolites. The challenge is to find out how they work together to regulate cellular responses to external and internal cues. Computational models provide insight into the intricate relationships between stimuli and cellular responses. I first overview a suite of physics-based methods, known as Modular Response Analysis, which infer both direct causative connections and their strengths in cellular signaling and gene networks from perturbation data (https://www.ncbi.nlm.nih.gov/pubmed/12242336). Further, I show that drug resistance resulting from dimerization of kinases (such as, BRAF/CRAF, JAK2, etc) can be explained by allosteric inhibitor effects and the emergence of different drug affinities between free kinase monomers versus dimers (https://www.ncbi.nlm.nih.gov/pubmed/26344764). Finally, I overview an exciting and counterintuitive discovery made using a new type of mathematical modelling, which combines aspects of protein structure, posttranslational modifications, thermodynamics, and dynamic reaction mechanisms (https://www.ncbi.nlm.nih.gov/pubmed/30007540). We used model predictions to block oncogenic RAS signalling in metastatic melanoma cells. RAS is mutated in 30% of all human cancers, and RAS mutated cancers are clinically considered to be undruggable and resistant to current treatments. Our approach identified non-intuitive drug combinations that synergise to block critical RAS effector pathways. Website: http://www.ucd.ie/sbi/
https://people.ucd.ie/search/Kholodenko
schedule
11.30 - 12.30: LECTURE
University of Luxembourg
Maison du Savoir
2, avenue de l'Université
L-4365 Esch/Alzette
Auditorium: 3.350
Registration required for the Lecture - send us an email
programme 2018-2019
About the Lecture & Workshop series - TRANSLATIONAL BIOINFORMATICS AND SYSTEMS BIOMEDICINE
The LIH lecture and workshops series in Translational Bioinformatics and Systems Biomedicine, supported by the FNR and jointly organized with the University of Luxembourg, are gathering internationally
This lecture will be followed by a workshop especially dedicated to early-stage researchers.
Attendance to the lecture and workshop are free of charge. Should you be interested in registering for the workshop, please feel free to do so by sending us an email.