Design principles of complex cellular decision-making networks in cancer
Visiting speaker
Mohit Kumar Jolly
Associate Professor in Bioengineering at Indian Institute of Science, Bangalore, India.
Past Talk
Hybrid
Monday
Nov 11, 2024
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2:00 pm
EST
Virtual
177 Huntington Ave.
11th floor
Devon House
58 St Katharine's Way
London E1W 1LP, UK
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Elucidating the design principles of regulatory networks driving cellular decision-making is of fundamental importance in mapping and controlling cellular behaviour. Despite their size and complexity, large biological regulatory networks often lead to a limited number of cell-states/phenotypes. How this canalization is achieved remains largely elusive. Here, we investigated multiple different networks governing cell-state transition during cancer metastasis, and identified a latent design principle in their topology that limits their phenotypic repertoire – the presence of two “teams” of nodes engaging in a mutually inhibitory feedback loop. These "teams" are specific to these networks and directly shape the phenotypic landscape and consequently the cell-fate trajectories. Our analysis reveals that network topology alone can contain information about phenotypic distributions it can lead to, thus obviating the need to simulate them. We present experimental evidence of such "teams" in transcriptomic datasets across many contexts (cancer cell plasticity in breast cancer, melanoma, lung cancer etc.). Overall, we propose these “teams” as a network design principle that drive cell-fate canalization in diverse decision-making processes, and drastically reduce the dimensionality of the phenotypic space.
About the speaker
About the speaker
Mohit is an Associate Professor in Bioengineering at Indian Institute of Science, Bangalore. He obtained his B Tech and M Tech from IIT Kanpur and PhD from Rice University, all in Bioengineering. His group integrates multi-scale mathematical models, single-cell multi-omics analysis, and works in close collaboration with experimental cancer biologists and clinical oncologists, to understand the dynamics of phenotypic plasticity and heterogeneity driving cancer metastasis and drug resistance. He has served as the co-chair of Mathematical Oncology subgroup of Society for Mathematical Biology, and is the current Editor-in-Chief of NPJ Systems Biology & Applications. He also received 2022 Young Alumnus Award of IIT Kanpur, 2023 ICTP Prize and 2024 Young Engineering Alumnus Award, Rice University.
Mohit is an Associate Professor in Bioengineering at Indian Institute of Science, Bangalore. He obtained his B Tech and M Tech from IIT Kanpur and PhD from Rice University, all in Bioengineering. His group integrates multi-scale mathematical models, single-cell multi-omics analysis, and works in close collaboration with experimental cancer biologists and clinical oncologists, to understand the dynamics of phenotypic plasticity and heterogeneity driving cancer metastasis and drug resistance. He has served as the co-chair of Mathematical Oncology subgroup of Society for Mathematical Biology, and is the current Editor-in-Chief of NPJ Systems Biology & Applications. He also received 2022 Young Alumnus Award of IIT Kanpur, 2023 ICTP Prize and 2024 Young Engineering Alumnus Award, Rice University.