Systems Biology and Protease Networks in Tissue Destructive Diseases 

Proteases are enzymes that degrade other proteins and when they degrade extracellular matrix proteins, this can lead to tissue remodeling either for health or disease.  Our lab studies the activities of powerful proteases that degrade elastin and collagen in disease such as cancer metastasis, cardiovascular disease, tendinopathy and more.

Enzymes also follow certain mathematical rules that we can model computationally, and then we can model their activity to predict tissue damage in certain diseases.  The beauty of computational biology is that it can generate novel hypotheses, which we then validate experimentally. Validation of the predictions can then be done with biochemistry assays on the mutant enzymes.

If you are interested in biochemistry, enzymology, systems biology, or mathematical biology and coding, then this could be an interesting project and experience for you.

Our lab does a number of diseases, as you can see on our website linked, below, but proteases and their activity are at the heart of them all!

https://www.nibib.nih.gov/labs-at-nibib/section-mechanics-tissue-remode…

“Reassessing enzyme kinetics: Considering protease-as-substrate interactions in proteolytic networks” Ferrall-Fairbanks MC, Kieslich CA, Platt MO. Proc Natl Acad Sci U S A. 2020 Feb 11;117(6):3307-3318. doi: 10.1073/pnas.1912207117. Epub 2020 Jan

“Dynamic Model of Protease State and Inhibitor Trafficking to Predict Protease Activity in Breast Cancer Cells.” Shockey WA, Kieslich CA, Wilder CL, Watson V, Platt MO. Cell Mol Bioeng. 2019 Jun 19;12(4):275-288. doi: 10.1007/s12195-019-00580-5.