Advances in High-Throughput 3-D Multicellular Systems Biology

Friday, February 22, 2019 -
2:00pm to 3:00pm
The FUNG Auditorium
Paul Macklin

Associate Professor
Director of Undergraduate Studies
Intelligent Systems Engineering
Indiana University

Advances in High-Throughput 3-D Multicellular Systems Biology

Abstract: 

Diverse bioengineering problems—spanning from microbial colonies to tissue development and dysregulated tissues—require us to understand and engineer the behavior of multicellular systems. In these systems, multiple cell types live and communicate in complex biochemical and biomechanical environments. Computational models can act as "virtual laboratories" for multicellular systems biology. The ideal such laboratory would include cell and tissue biomechanics, biotransport of multiple chemical substrates including signaling factors, and many interacting cells. In this talk, we will introduce PhysiCell (http://dx.doi.org/10.1371/journal.pcbi.1005991), an open source agent-based platform for 3-D multicellular systems biology. With this platform, desktop workstations can routinely simulate systems of ten or more cell-secreted chemical signals and tissue substrates, along with 10^5 to 10^6 individual cells that grow, divide, die, secrete chemical signals, move, exchange mechanical forces, and remodel their tissue microenvironment.

We will explore PhysiCell models to investigate (1) the role of ECM remodeling and hypoxia in breast cancer invasion, (2) how mechanical interactions between cancer cells and the liver parenchyma can affect the successful seeding of cancer metastases, (3) potential designs for synthetic multicellular systems that transport cancer therapeutics, (4) possibilities for pH-driven cancer nanotherapies, and (5) the critical role of stochastic tumor-immune interactions in cancer immunosurveillance. We will also discuss our recent work to improve the usability and utility of high-performance agent-based models, including machine learning-driven model exploration on supercomputing resources, methods to transform complex command-line models to user-friendly, interactive cloud-hosted simulators, and ad hoc crowdsourcing for small teams. We’ll close by discussing the future outlook for using high-throughput multicellular simulations to efficiently explore high-dimensional design spaces and accelerate discovery.

 

Bio: 

Paul Macklin is a mathematician, Associate Professor, and Director of Undergraduate studies in the newly-established Department of Intelligent Systems Engineering at Indiana University. His lab works with teams of biologists, modelers, and clinicians to develop and validate sophisticated computer models of multicellular systems, with a focus on cancer, tissue engineering, and synthetic systems. To drive this work, his lab develops open source tools for 3-D multicellular systems biology, including BioFVM (multi-substrate diffusive transport) and PhysiCell (off-lattice agent-based modeling). His lab also develops techniques to ease the use and increase the utility of agent-based modeling, including machine learning-driven model exploration, high-throughput investigations, ad hoc small team crowdsourcing, and cloud-hosted interactive simulators.