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ISCBacademy - Crossing scales from molecules to cells to patient with systems biology

Hosted by: ISCB
Venue: N/A
Dates: Feb 20, 2024 through Feb 20, 2024

Systems biology has been widely used to study signalling in immune cells. Multiscale modelling approaches have provided insight into how cellular signalling leads to distinct cell fates, which control the immune response. Less attention has been paid to what happens to these networks, cell fates and patient outcomes when signalling is impacted by mutations. B cell lymphoma is a highly heterogeneous disease and treatment progress has been challenged by patient-to-patient variability. The Mitchell lab is asking whether systems biology models can enable us to overcome this patient-to-patient heterogeneity and get the right drugs to the right patients. Through combined computational modelling and experimental work, we found that mutations cause “crossed wires” within molecular signalling that result in tumour cells misinterpreting their microenvironment. We found that when mutations impact multiple signalling networks that control multiple cell fates, the resultant changes in cellular proliferation can be greater than expected. We find that by combining DNA sequencing data with ordinary differential equation models we can create heterogeneous populations of virtual patients. Within these patients, we computationally identify a new subgroup of patients who have co-occurring dysregulation of their cell cycle and apoptosis. We find the perturbed signalling within these patients results in dismal outcomes (progression-free survival). We need new treatment approaches for these patients. By simulating the impact of inhibitors within these molecular networks we find we can predict which inhibitors are most effective in each lymphoma cell population. Validating these predictions in the lab demonstrates how computational systems biology approaches are unlocking a personalized medicine approach to getting the right drugs to the right patients.
Additional Information
Event URL: https://www.iscb.org/iscbacademy
ISCB Member Discount: TBA

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