Yin, John

BA (Liberal Arts) Columbia College
BS (Chemical Engineering) Columbia University
PhD (Chemical Engineering) University of California, Berkeley
Post-doctoral Fellowship (Biochemical Kinetics) Max-Planck-Institut fuer Biophysikalische Chemie, Goettingen, Germany

Fields of Interest

virus-host interactions
systems biology
microfluidics
pre-biotic chemistry

Publications

You, L., and Yin, J. (2001). Simulating the growth of viruses. Pac Symp Biocomput, 532-543.
Duca, K. A., Lam, V., Keren, I., Endler, E. E., Letchworth, G. J., Novella, I. S., and Yin, J. (2001). Quantifying viral propagation in vitro: toward a method for characterization of complex phenotypes. Biotechnology Progress 17, 1156-1165.
You, L., and Yin, J. (2002). Dependence of epistasis on environment and mutation severity as revealed by in silico mutagenesis of phage T7. Genetics 160, 1273-1281.
You, L., Suthers, P., and Yin, J. (2002). Effects of Escherichia coli physiology on the growth of phage T7 in vivo and in silico. Journal of Bacteriology 184, 1888-1894.
Middleton, J. K., Severson, T. F., Chandran, K., Gillian, A. L., Yin, J., and Nibert, M. L. (2002). Thermostability of reovirus disassembly intermediates (ISVPs) correlates with genetic, biochemical, and thermodynamic properties of major surface protein mu1. J Virology 76, 1051-1061.
Srivastava, R., You, L., Summers, J., and Yin, J. (2002). Stochastic versus deterministic modeling of intracellular viral kinetics. J. Theoretical Biology 218, 309-321.
You, L., Hoonlor, A., and Yin, J. (2003). Modeling biological systems using Dynetica---a simulator of dynamic networks. Bioinformatics 19, 435-436.
Endler, E. E., Duca, K. A., Nealey, P. F., Whitesides, G. M., and Yin, J. (2003). Propagation of viruses on micropatterned host cells. Biotechnol Bioeng 81, 719-725.
Kim, H., and Yin, J. (2004). Energy-efficient growth of phage Q&beta in Escherichia coli. Biotechnol Bioeng 88, 148-156.
Yin, J. (2004). Genome function--a virus-world view. Adv Exp Med Biol. 547:31-46.
Kim, H., and Yin, J. (2004). Quantitative analysis of a parasitic antiviral strategy. Antimicrobial Agents & Chemotherapy 48, 1017-1020.
Lim, K. I., Narayan, S., Young, J. A., and Yin, J. (2004). Effects of lipid rafts on dynamics of retroviral entry and trafficking: quantitative analysis. Biotechnol Bioeng 86, 650-660.
Haseltine, E., Rawlings, J., and Yin, J. (2005). Dynamics of viral infections: incorporating both the intracellular and extracellular levels. Computers and Chemical Engineering 29, 675-686.
Endler, E., Nealey, P., and Yin, J. (2005). Fidelity of micropatterned cell cultures. Journal of Biomedical Materials Research A 74, 92-103
Lam, V., Duca, K. A., and Yin, J. (2005). Arrested spread of vesicular stomatitis virus infections in vitro depends on interferon-mediated antiviral activity. Biotechnol Bioeng 90, 793-804.
Lim, K. I., and Yin, J. (2005). Localization of receptors in lipid rafts can inhibit signal transduction. Biotechnol Bioeng 90, 694-702.
Kim, H., and Yin, J. (2005). In silico mutagenesis of RNA splicing in HIV-1. Biotechnol Bioeng, 91(7), 877-93.
Kim, H., and Yin, J. (2005). Robust growth of human immunodeficiency virus type 1 (HIV-1). Biophysical Journal, 89(4), 2210-21.
Kim, H., and Yin, J. (2005). Effects of RNA Splicing and Posttranscriptional Regulation on HIV-1 Growth: a Quantitative and Integrated Perspective. IEE Proceedings-Systems Biology, 152(3), 138-152.
Napier, J., and Yin, J. (2006). Formation of Peptides in the Dry State. Peptides, 27(4):607-10.
Lim, K. and Yin, J. (2006). Dynamic tradeoffs in the raft-mediated entry of human immunodeficiency virus type 1 into cells, Biotechnol Bioeng 93(2):246-57.
Lam, V., Boehme, K.W., Compton, T. and Yin, J. (2006) Spatial Patterns of Protein Expression in Focal Infections of Human Cytomegalovirus. Biotechnol Bioeng,93(6):1029-39.
You, L. and Yin, J. (2006) Evolutionary Design on a Budget: Robustness and Optimality of Bacteriophage T7. IEE Proc. Systems Biology, 153(2), 46-52.
Lim, K., Lang, T., Lam, V. and Yin, J. (2006). Model-based Design of Growth-attenuated Viruses, PLoS Computational Biology, 2(9): e116.
Zhu, Y. and Yin, J. (2007). A quantitative comet assay: imaging and analysis of virus plaques formed with a liquid overlay, Journal of Virological Methods, 139, 100-102.
Middleton, J.K, Agostod, M.A., Severson, T.F., Yin, J., Nibert, M.L. (2007), Thermostabilizing mutations in reovirus outer-capsid protein mu1 selected by heat inactivation of infectious subvirion particles, Virology, 361(2):412-25.
Agosto M.A., Middleton J.K., Freimont E.C., Yin J., Nibert M.L. (2007), Thermolabilizing Pseudoreversions in Reovirus Outer-Capsid Protein mu1 Rescue the Entry Defect Conferred by a Thermostabilizing Mutation, J Virol., 81(14):7400-9.
Suthers, P., Gourse, R., Yin, J. (2007), Rapid Responses of Ribosomal RNA Synthesis to Nutrient Shifts, Biotech. Bioeng, 97(5):1230-45.
Yin, J. (2007), Chemical Engineering and Virology: Challenges and Opportunities at the Interface, AIChE Journal, Sept 2007.
Abedon S.T., Yin J. (2008). Impact of Spatial Structure on Phage Population Growth, in Bacteriophage Ecology: Population Growth, Evolution, and Impact of Bacterial Viruses, Cambridge University Press.
Haseltine, E.L., Yin, J., Rawlings, J.B. (2008), Implications of Decoupling the Intracellular and Extracellular Levels in Multi-level Models of Virus Growth, Biotech. Bioeng, in press.
Haseltine, E.L., Lam, V., Yin, J., Rawlings, J.B. (2008), Image-Guided Modeling of Virus Growth and Spread, Bulletin of Mathematical Biology, in press.

Selected Awards, Honors and Societies

Robert Emmett Dolan Prize, supporting cello studies at Juilliard School of Music, New York (1978-1983)
Alexander von Humboldt Fellow, Germany (1988)
NSF Young Investigator Award (1994)
NSF Presidential Early Career Award for Scientists and Engineers (PECASE) (1996)

Post-doctoral Openings in Systems Biology (starting Spring/Summer 2008)

What might you gain while pursuing post-doctoral research in the Yin lab?

(1) Hands-on training in the emerging and exciting area of systems biology, focusing on virus-host interactions,

(2) Experience in how to integrate research, teaching and learning (see www.delta.wisc.edu) --- skills that are highly valued by academic employers and funding agencies,

(3) Guidance by a mentor who has a strong record of placing students and post-docs in stimulating academic (Caltech, Duke, Harvard, MIT, Stanford, Tufts, UConn-Storrs, UC-Berkeley), government, and industry positions,

(4) Opportunities for personal growth at a world-class university, located in safe, attractive and affordable city surrounded by beautiful lakes.

We are advancing new technologies to better understand the growth, spread and evolution of viruses. Active NIH-supported projects are in three areas: (1) flow-enhanced spread and characterization of infections in microfluidic devices, (2) phenotype distributions from measurements and models of infections initiated by single virus particles, (3) dynamics of virus populations in anti-viral environments. Systems of current interest are influenza virus and vesicular stomatitis virus. The most competitive applicants will be exceptionally creative, highly-motivated individuals with experience in:

Quantitative biology: methods to detect and/or quantify nucleic acids, proteins, viruses, virus-like particles, activation of innate immunity. Experience in microscopy, construction or characterization of live-cell reporters of gene expression, quantitative imaging and image analysis would be especially valuable

Engineering or physical sciences: modeling or simulation of reactive systems, fluid and particle dynamics, or microfluidics, with emphasis on the development of data-driven mechanistic models. Experience in parameter estimation, sensitivity analysis and model-discrimination would be especially valuable

Madison, Wisconsin routinely ranks at the top of national surveys of 'best places to live,' and post-docs here thrive on a rich diversity of outdoor and cultural opportunities. Forward your CV with cover letter, and have three letters of reference sent to John Yin by e-mail (yin@engr.wisc.edu), fax (608/262-5434) or regular mail: Department of Chemical and Biological Engineering, University of Wisconsin, Madison, WI 53706-1607 USA.

Summary

Viruses are remarkable products of evolutionary design. As sub-microscopic particles (diameters 20 to 300 nanometers) viruses encode functions that instruct their explosive production, making thousands of virus progeny within an infected cell. These infections can ultimately cause diseases of biomedical, biodefensive, and economic importance including AIDS, cancer, influenza, the common cold and hemorrhagic fever in humans, and foot-and-mouth disease in livestock.

My co-workers and I are pursuing research at the interface between virology and engineering. We aim to advance new experimental methods and computer simulations to better understand how viruses grow, how they spread, and how they evolve. A long-term goal is to elucidate mechanisms by which viruses cause disease and thereby enable the development of robust of anti-viral strategies.

Our computational models aim to reveal how the growth rate of a virus depends on the kinetics of its constituent biochemical reactions, incorporating genetic, biochemical and biophysical data from diverse laboratory experiments performed over the last four decades. To date we have developed detailed mechanistic computer simulations for the intracellular growth of viruses that infect bacteria (phage T7 and phage Q&beta) and mammalian hosts (HIV-1). Our simulations account for the mechanisms and rates of essential processes such as virus entry, transcription, translation, genome replication, assembly and release of progeny viruses. They also increasingly account for the effects of viral infection on host biosynthetic resources, and host defensive responses to infection. From such studies we are beginning to gain insights into how the encoded functions within a small genome (virus) interact with its environment (host cell) to define a minimal developmental process (virus growth and spread). We are currently expanding these approaches to study vesicular stomatitis virus (VSV), a virus that is prototypical of a broad class of RNA viruses (e.g., rabies, respiratory syncytial, ebola), and VSV-based viruses have potential applications as HIV-1 vaccines and anti-tumor therapeutics.

In the lab we are advancing methods to quantitatively study the dynamics of virus growth over single and multiple infection cycles. Our approaches include measurements of virus production from single infected cells, using fluorescence-activated cell sorting, as well as population-level measures of virus production from synchronized cell infections. To track the dynamics of virus populations over multiple infection cycles we are developing a method of spreading focal infections. This method initiates virus infections at a point within a host-cell monolayer and tracks the growth and spatial spread of viruses using fluorescence microscopy and digital imaging.

Our virus studies described above emphasize a 'top-down' approach to complex biology. Take a highly adapted phenomenon (virus infection cycle) and try to understand how the parts work as an integrated system. We are also pursuing 'bottom-up' studies, aiming to design experiments that allow biological properties to emerge from purely chemical systems. Of special interest would be molecules that facilitate their own synthesis. Toward this end we have begun to identify minimal conditions that enable the spontaneous formation of stable bonds between simple building blocks (amino acids).

Copyright 2008 The Board of Regents of the University of Wisconsin System
Date last modified: 13-May-2008
Content by: yin@engr.wisc.edu
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