AIMRC Seminar: Pilot Project Research on Epigenome Engineering and Tumor Cell Bioenergetics

From left: assistant professors Chris Nelson, Kevin Murach and Jian Zhang

The Arkansas Integrative Metabolic Research Center (AIMRC) will host previous pilot project awardees — assistant professors Chris Nelson, Kevin Murach and Jian Zhang — at 12:55 p.m. on Wednesday, Sept. 18, in Bell Engineering 2267. In this talk, they will discuss the results of their research. Two projects will be discussed:

Project Title: Epigenome engineering for precise genetic perturbation of skeletal muscle gene expression and metabolism (Nelson/Murach)
Abstract: Mechanisms of many complex diseases that impact skeletal muscle function, aging and metabolism remain elusive. Recent advances in genome engineering tools have provided methods for precise gene activation and gene silencing. These tools have enabled functional genomic screening of the non-coding genome and high-throughput screening of gene regulatory elements at an unprecedented scale. Mice that allow inducible expression of these tools will allow higher throughput study of individual genes that contribute to muscle metabolism and overall health and enable multiplex genetic screening. In this project, we establish these mouse lines at the U of A and demonstrate the flexibility of genetic screening provided by these models. The result of this work will be a powerful new genetic screening tool with high collaborative potential and a robust proof-of-concept dataset for follow-on funding.

Project Title: Investigating the bioenergetics of tumor cell clustering and cell-cell interactions (Zhang)
Abstract: Clustering and inter-cellular interactions often make tumor cell clusters and micrometastases more invasive, proliferative and survive better than individual tumor cells. While it is known that micrometastases exhibit distinct metabolic programs compared to primary tumor cells in breast cancer and that cancer cells can adapt their metabolism to the local tumor microenvironment, it is not clear whether this metabolic adaptation is related to cell clustering. This project proposed to engineer the size, shape, composition and cell-cell interaction of cell clusters using micropatterning, microfabrication and biological interventions, and use these engineered clusters to systematically assess the regulation of tumor bioenergetics by cell clustering. As therapeutics that are effective for single cells may not work for tumor cell clusters, the successful completion of this project and future work will allow the development of efficient cancer therapies to counter cancers as they relate to tumor cellclustering, micrometastasis, metabolic adaptation and therapeutic resistance.

This event is supported by NIGMS of the National Institutes of Health under Award Number P20GM139768. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Pizza and beverages will be served. Please contact Kimberley Fuller, fullerk@uark.edu, for more information.

For those unable to attend in person, this seminar will also be available via Zoom.