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Paul Joyce

University of Idaho


Funding


 
Grant Number
NIH-R01 GM076040-01   
Title
Patterns of Adaptive Evolution
Principal Investigator
Paul Joyce
Co Principal Investigator
 H.A. Wichman
Budget
$ 1,369, 805
Years Funded
2006-2011

Brief Description

Evolution by natural selection (adaptive evolution) is one of the major generalizations in biology. It also has important ramifications for medicine, agriculture, and biotechnology. Unfortunately, many outcomes of natural selection have been to our detriment. The most obvious ones are apparent in medicine - the evolution of drug-resistant bacteria and viruses, to the point that some infections are now untreatable. Yet, whatever problems arise from natural selection of pests and parasites, we need not remain as helpless victims to its effects: understanding evolution offers potential solutions. Our ability to predict adaptive evolution is still in its infancy. Yet it is now apparent that many opportunities exist for improving that understanding, aided by statistical modeling of molecular data.  This proposal integrates theoretical and experimental methods to explore properties of adaptive evolution. 

 

While it might seem that the characteristics of beneficial mutations will vary idiosyncratically from system to system, recent work using statistical theory suggests that there may indeed be generalities that transcend the biological details of a system. Exploring the nature of these generalities is the main focus of this proposal.  Both the theory and experiments developed in this proposal may also suggest useful approaches to predict the trajectory of evolution in organisms of medical importance. Such information could be extremely useful at early stages of drug development, as well as in designing treatments that are more resilient to evolution in the target species.  


 
Grant Number
NIH COBRE T1
Title
Interdisciplinary study of viral host switching
Principal Investigator F.M. Ytreberg
Co Principal Investigators P. Joyce and H.A. Wichman
Budget 918,999.00
Years Funded 8/01/09-7/29/11


Brief Description

A major challenge for public health officials is predicting the outbreak of diseases. Zoonotic diseases are a
particular challenge since little is known about the specific mechanisms behind host switching. For example,
what abiotic factors increase the probability of host switching? The proposed research is an interdisciplinary
investigation that will provide insight into the mechanisms behind viral host switching. Our central
hypothesis, which is based on preliminary results from our current research, is that viral adaptation to small
increases in temperature enhances capsid stability, which in turn increases the likelihood of viral host
switching. We are interested in differences in temperature of a few degrees, such as the difference between
mammalian and avian body temperature, or the change that might occur in parts of the world due to global
warming. This is a highly interdisciplinary study that brings together a computational biophysicist, an
evolutionary biologist and a statistician for a multipronged attack on a hypothesis that could have major
implications for human health. We will test our central hypothesis via the following specific aims: (i) Use
experimental evolution to test the hypothesis that viruses carrying adaptive mutations for increased
temperature are more likely to switch hosts than the wild type viruses. (ii) Use biophysical modeling to test
the hypothesis that some mutations involved in viral host switching increase the stability of the capsid. (iii)
Use statistical and spatial modeling to explore the probability of host switching and the dynamics of spread in
a spatially heterogeneous environment.