RESEARCH INTERESTS
I am currently working as a post-doctoral researcher in the group
of Rob J. De Boer at Utrecht University (The Netherlands). I am
using mathematical models to get better insights into how immune system
(in particular, CD8 and CD4 T cell response to viruses and bacteria)
works. For a relatively complete list of pulications search Pubmed
(or see Publications or CV). The specific projects I
am spending my time (or previously
worked) on include the following:
Quantifying cell turnover rate using CFSE data
- What are the rates of cell division and death during an immune
response? What is the turnover rate of memory CD8 and CD4 T cells or
expanding populations of
antigen-specific T cells? We analyze how these questions can be
answered by using a new label CFSE that allows to quantify the number
of
divisions a given cell has undergone. We do this by developing
mathematical models and applying these models to the CFSE data. To see
some currently available tools for fitting CFSE data, click here.
The dynamics of immune responses
- Many infections are harmful to their hosts but is this harm due
to the
microbe itself or is it mediated by the immune response? Although this
question is fairly simple (well, maybe not), we don't know the answer
to it for most infections. Although there might be some ways to check
whether the specific immune response is involved into pathogenesis for
some animal model infections (using knockouts), for many infections of
humans it is not so simple. One possibility might be to measure the
life-span of virus-infected cells and see whether immune response, or
more precisely, the efficiency of the immune response may affect the
life-span of virus infected cells.
- For other projects on this topic, see CV.
Evolution of microparasites and
the
maintenance of parasite virulence (ph.D. thesis, Emory University)
One of the fascinating questions in current evolutionary biology is to
explain why there are so many parasites and why many of them are
virulent. Virulence in this case is understood as the reduction of
host fitness due to presence of the parasite. In many cases
pathogenesis of microparasites is simply coincidental (botulism,
tetanus) whereas in others there seems to be a positive correlations
between how efficiently the parasite is transmitted and how virulent
(i.e. how much harm it causes to its hosts) the parasite
is. Evolutionary theory predicts that if there are this kind of
trade-offs (correlations) between transmissibility and virulence of
parasites then parasites with some intermediate level of virulence are
selected (at which the basic reproductive number, Ro, is
maximized). Using simple mathematical models describing the
within-host dynamics of microparasites causing acute infections in
vertebrate hosts, I am investigating the factors that influence the
evolution of such microparasites.
- host heterogeneity. One of the factors that is thought to
affect the
evolution of parasites is heterogeneity of the host population. Host
heterogeneity is generally understood in terms of trade-offs that
hosts impose on infecting them parasites: a given parasite by adapting
to one host type (and gains transmission from that host type) weakens
its ability to replication in hosts of other types (and therefore
loses transmission in these hosts). In our work we investigate what
happens in host heterogenetiy does not impose any trade-offs on
parasites. We find that higher levels of host heterogeneity may
actually lead to higher levels of mortality in the host population
(and therefore virulence).
- robustness. How robust are simple within-host models to changes
in the model
assumptions? Can we predict the direction of parasite evolution? Do
details of the within-host dynamics of the parasite and the immune
system matter for the prediction of the evolution of microparasites? We
address these questions by changing the assumption of the simple
within-host model and see how changes in the assumptions of the model
affect the optimal level of virulence parasites evolve. In particular,
we change two characteristics that we believe are the most important
in parasite fitness: the rate of parasite transmission from infected
hosts and the mechanism of parasite pathogenesis. We find that changes
in the assumptions of these simple models lead to high changes in the
optimal virulence parasites evolve.
Population dynamics of bacterial
plasmids (Master thesis, Krasnoyarsk State University,
candidate of sciences
in physics and math, Institute
of Biophysics)
Work in this direction started during my graduate studies at Krasnoyarsk State University (Department
of Biophysics) and at the Institute
of Biophysics, Siberian Branch
of Russian Academy of Sciences. We (together with my former advisor
Anatoly Brilkov) have been asking the following questions:
- how the
expression of plasmid genes may affect the stability of
plasmid-bearing cells during continuous cultivation in chemostat and
serial passage culture;
- how the presence of several copies of a
plasmid in
a given cell influences the dynamics of plasmid-bearing strains
and their plasmid-free counterparts.
Evolution criteria for model
ecological systems (bachelor's thesis, Krasnoyarsk State University)
A consideration of Darwinian evolution in a closed ecological system
leads to an apparent contradiction: the fittest individuals can destroy
the ecosystem if they grow indefinitely. Since in a closed ecological
system the total biomass is limited all links of the biotic cycle of
an ecosystem must evolve in accord. Using simple
mathematical models we considered a competition of such ecosystems
evolving by maximization of the total production and found that
introduction of consumers leads to an increase of the total production
comparing to the simple cycle without consumer (advisors Anatoly
Brilkov, Nicolay Pechurkin and Alexei Babkin).
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