|
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.
|
