Professor Richard Goldstein

Professor of Pathogen Evolution

About

Research in the Goldstein lab focuses on computational modelling of pathogen evolution, with an emphasis on viruses.

Research summary

In order to understand the properties of viruses, how they transmit, how they interact with their hosts, how they transfer between hosts, we need to investigate the evolutionary process that determined their form and function. Conversely, the evolution of viruses and hosts cannot be understood without considering how their form and function constrain the evolutionary process. Finally, the evolutionary record encodes the history of these organisms - when and where they emerged, how they spread amongst various populations, how they adapted to new hosts (such as humans), and how they have interacted with host factors, immune system, and drugs. Analysis of these sequences can provide a powerful window into this history, providing insight into the present situation and future trends. This has important consequences for monitoring and controlling disease emergence and spread, for identifying new drug targets, for modelling the emergence of drug resistance, as well as for developing our basic understanding of viruses and virus-host interactions. 

We are engaged in three interrelated topics:

1. How do we understand the evolution of macromolecules such as genes and proteins? Using simple models of evolution, we try to develop a conceptual model for understanding the underlying evolutionary process, including the way the process depends upon its dynamically-changing context, that matches the growing available data on evolutionary change.
2. How can we use our understanding of macromolecular evolution to construct more realistic and informative models of evolutionary change? How can we construct models that allow us to better investigate the biology of the evolving systems, such as characterising the selective constraints acting on the genes and proteins, and how these change?
3. How can we apply these new models to important pathogens? How do we use these models to understand the interaction of viruses with their hosts, and how these interactions change when viruses jump hosts, particularly to humans? How do we determine transmission pathways, a matter of significance to public health efforts?

This work takes advantage of our placement in the Division of Infection and Immunity at UCL, providing us with a wealth of collaborative opportunities.

Selected publications

• Goldstein RA, Pollock DD. Sequence entropy of folding and the absolute rate of amino acid substitutions. Nat Ecol Evol. 2017;1:1923-1930
• Ruis C, Roy S, Brown JR, Allen DJ, Goldstein RA, Breuer J. The emerging GII.P16-GII.4 Sydney 2012 norovirus lineage is circulating worldwide, arose by late-2014 and contains polymerase changes that may increase virus transmission. PLoS One. 2017;12:e0179572
• Godány M, Khatri BS, Goldstein RA. Optimal chemotactic responses in stochastic environments. PLoS One. 2017;12:e0179111
• Thiltgen G, Dos Reis M, Goldstein RA. Finding Direction in the Search for Selection. J Mol Evol. 2017;84:39-50
• Sutherland KA, Collier DA, Claiborne DT, Prince JL, Deymier MJ, Goldstein RA, Hunter E, Gupta RK. Wide variation in susceptibility of transmitted/founder HIV-1 subtype C Isolates to protease inhibitors and association with in vitro replication efficiency. Sci Rep. 2016;6:38153
• Goldstein RA, Pollock DD. The tangled bank of amino acids. Protein Sci. 2016;25:1354-62
• Khatri BS, Goldstein RA. Simple Biophysical Model Predicts Faster Accumulation of Hybrid Incompatibilities in Small Populations Under Stabilizing Selection. Genetics. 2015;201:1525-37
• Khatri BS, Goldstein RA. A coarse-grained biophysical model of sequence evolution and the population size dependence of the speciation rate. J Theor Biol. 2015;378:56-64
• Goldstein RA, Pollard ST, Shah SD, Pollock DD. Nonadaptive Amino Acid Convergence Rates Decrease over Time. Mol Biol Evol. 2015;32:1373-81
• Monit C, Goldstein RA, Towers G, Hué S. Positive Selection Analysis of Overlapping Reading Frames Is Invalid. AIDS Res Hum Retroviruses. 2015;31:947.