Chris Bystroff


My lab studies the folding and design of proteins, enzymes, vaccine antigens, and biosensors. When I came here in 1999, I was a bioinformaticist and my lab worked exclusively in computational biology. Since then, we have evolved into a mostly experimental lab, with a little computation still mixed in. Our early work included algorithm development in protein structural bioinformatics, including structure prediction, contact map prediction, local structure prediction, hidden Markov models, sequence alignment, molecular surface area calculation, torsion space molecular dynamics, simplified representations for molecular dynamics, bioinformatics-driven force fields, structure-based alignment, and models for folding pathways. We proposed the "phone cord effect" to explain superhelicity in alpha helical crossovers. 
Starting about ten years ago, we began doing experimental work on green fluorescent protein (GFP) with the help of molecular biologist Prof.  Donna E. Crone. We created a non-circularly permuted "re-wired" GFP, a permuted and truncated "leave-one-out" GFP, a variant that folds faster and more efficiently, and a GFP-base biosensor. We inserted strategically-placed disulfides to test specific hypotheses for the folding pathway of GFP and reasoned out the presence of two specific folding intermediates. More recently we are studying the formation of the fluorescent chromophore and the dependence of GFP fluorescence on specific residues and on thermodynamic stability. 
The principle thrust of the lab is to develop the leave-one-out (LOO) method for GFP-based biosensors. By combining computational design and high throughput screening, we find sets of mutations that complement a specific bound peptide and allow the truncated LOO-GFP to fold and glow only in the presence of a target protein which has been unfolded to expose that sequence. A biosensor for detection of H5N1 influenza virus hemagglutinin was published in 2015. We are collaborating on the development of a sensor for dengue virus and putting those sensors on protein fibers.
We are also engaged in a collaborative effort to develop a contraceptive vaccine. The vaccine will produce temporary and reversible infertility. Instead of having to take an action to be protected, you will be protected by default, and would need to take an action to be temporarilly fertile again. The vaccine targets the sperm-specific calcium channel CatSper, which is required for sperm hyperactive motility and therefore for fertility. Sperm antigens are placed on the surface of non-infectious virus-like particles (VLP) for vaccination.
A contraceptive vaccine is a humane way to deal with global overpopulation. Overpopulation is widely believed to be the root cause of anthropogenic climate change, overfishing, fresh water depletion, war, famine etc. -- in short, overpopulation is an existential threat. I recently published a computational model, called World4, for global population, predicting that a peak is coming soon. The good news is that by making every child a wanted child, population growth can be stopped humanely.
My lab is using chimeric constructs of Human Papilloma Virus (HPV) L1 protein as a self-assmbling virus-like nanoparticle. Theses particle raise strong immunity to epitopes on their surface. We are placing CatSper loops on the surface for a contracpetive vaccine, SARS-CoV2 spike protein loops on the surface as a glycan-free COVID vaccine, and metastatic cancer biomarkers for a late-stage cancer immunotherapeutic. This versatile chimeric-HPV technology has many applications in epitope-directed vaccine design.
This work was made possible by our collaborators, the Center for Computational Innovation (CCI), and Center for Biotechnology and Interdisciplinary Sciences (CBIS), and by grants from the NSF, NIH, Rosetta Commons, and a private foundation.


Other Focus Areas

bioinformatics, computational biology, biosensor design, vaccine design, protein structure motifs, population, contraception, systems dynamics


The following is a selection of recent publications in Scopus. Chris Bystroff has 68 indexed publications in the subjects of Biochemistry, Genetics and Molecular Biology, Computer Science, and Mathematics.

Jae Yeon Hwang, Shoaib Nawaz, Jungmin Choi, Huafeng Wang, Shabir Hussain, Mehboob Nawaz, Francesc Lopez-Giraldez, Kyungjo Jeong, Weilai Dong, Jong Nam Oh, Kaya Bilguvar, Shrikant Mane, Chang Kyu Lee, Christopher Bystroff, Richard P. Lifton, Wasim Ahmad, Jean Ju Chung
Frontiers in Cell and Developmental Biology
, 9
, 2021
Julia Koehler Leman, Brian D. Weitzner, Steven M. Lewis, Jared Adolf-Bryfogle, Nawsad Alam, Rebecca F. Alford, Melanie Aprahamian, David Baker, Kyle A. Barlow, Patrick Barth, Benjamin Basanta, Brian J. Bender, Kristin Blacklock, Jaume Bonet, Scott E. Boyken, Phil Bradley, Chris Bystroff, Patrick Conway, Seth Cooper, Bruno E. Correia, Brian Coventry, Rhiju Das, René M. De Jong, Frank DiMaio, Lorna Dsilva, Roland Dunbrack, Alexander S. Ford, Brandon Frenz, Darwin Y. Fu, Caleb Geniesse, Lukasz Goldschmidt, Ragul Gowthaman, Jeffrey J. Gray, Dominik Gront, Sharon Guffy, Scott Horowitz, Po Ssu Huang, Thomas Huber, Tim M. Jacobs, Jeliazko R. Jeliazkov, David K. Johnson, Kalli Kappel, John Karanicolas, Hamed Khakzad, Karen R. Khar, Sagar D. Khare, Firas Khatib, Alisa Khramushin, Indigo C. King, Robert Kleffner, Brian Koepnick, Tanja Kortemme, Georg Kuenze, Brian Kuhlman, Daisuke Kuroda, Jason W. Labonte, Jason K. Lai, Gideon Lapidoth, Andrew Leaver-Fay, Steffen Lindert, Thomas Linsky, Nir London, Joseph H. Lubin, Sergey Lyskov, Jack Maguire, Lars Malmström, Enrique Marcos, Orly Marcu, Nicholas A. Marze, Jens Meiler, Rocco Moretti, Vikram Khipple Mulligan, Santrupti Nerli, Christoffer Norn, Shane Ó’Conchúir, Noah Ollikainen, Sergey Ovchinnikov, Michael S. Pacella, Xingjie Pan, Hahnbeom Park, Ryan E. Pavlovicz, Manasi Pethe, Brian G. Pierce, Kala Bharath Pilla, Barak Raveh, P. Douglas Renfrew, Shourya S.Roy Burman, Aliza Rubenstein, Marion F. Sauer, Andreas Scheck, William Schief, Ora Schueler-Furman, Yuval Sedan, Alexander M. Sevy, Nikolaos G. Sgourakis, Lei Shi, Justin B. Siegel, Daniel Adriano Silva, Shannon Smith, Yifan Song
Nature Methods
, 17
, 2020
, pp.665-680
Julia Koehler Leman, Brian D. Weitzner, P. Douglas Renfrew, Steven M. Lewis, Rocco Moretti, Andrew M. Watkins, Vikram Khipple Mulligan, Sergey Lyskov, Jared Adolf-Bryfogle, Jason W. Labonte, Justyna Krys, Christopher Bystroff, William Schief, Dominik Gront, Ora Schueler-Furman, David Baker, Philip Bradley, Roland Dunbrack, Tanja Kortemme, Andrew Leaver-Fay, Charlie E.M. Strauss, Jens Meiler, Brian Kuhlman, Jeffrey J. Gray, Richard Bonneau
PLoS Computational Biology
, 16
, 2020
Megan Kizer, Ian D. Huntress, Benjamin D. Walcott, Keith Fraser, Christopher Bystroff, Xing Wang
, 58
, 2019
, pp.1332-1342
William F. Hooper, Benjamin D. Walcott, Xing Wang, Christopher Bystroff
BMC Bioinformatics
, 19
, 2018
Shounak Banerjee, Christian D. Schenkelberg, Thomas B. Jordan, Julia M. Reimertz, Emily E. Crone, Donna E. Crone, Christopher Bystroff
, 56
, 2017
, pp.736-747
Christian D. Schenkelberg, Christopher Bystroff
, 32
, 2016
, pp.1454-1461
Abhijit N. Shirke, Danielle Basore, Samantha Holton, An Su, Evan Baugh, Glenn L. Butterfoss, George Makhatadze, Christopher Bystroff, Richard A. Gross
Applied Microbiology and Biotechnology
, 100
, 2016
, pp.4435-4446

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