Michael A. Gilchrist

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Mathematical models of HIV-1 infection can help interpret drug treatment experiments and improve our understanding of the interplay between HIV-1 and the immune system. We develop and analyze an age- structured model of HIV-1 infection that allows for variations in the death rate of productively infected T cells and the production rate of viral particles as(More)
We present and analyse a model of protein translation at the scale of an individual messenger RNA (mRNA) transcript. The model we develop is unique in that it incorporates the phenomena of ribosome recycling and nonsense errors. The model conceptualizes translation as a probabilistic wave of ribosome occupancy traveling down a heterogeneous medium, the mRNA(More)
In this study we introduce a mechanistic framework for modeling host-parasite coevolution using a nested modeling approach. The first step in this approach is to construct a mechanistic model of the parasite population dynamics within a host. The second step is to define an epidemiological model which is used to derive the fitness functions for both the(More)
MOTIVATION To identify accurately protein function on a proteome-wide scale requires integrating data within and between high-throughput experiments. High-throughput proteomic datasets often have high rates of errors and thus yield incomplete and contradictory information. In this study, we develop a simple statistical framework using Bayes' law to(More)
Virus evolution during infection of a single individual is a well-known feature of disease progression in chronic viral diseases. However, the simplest models of virus competition for host resources show the existence of a single dominant strain that grows most rapidly during the initial period of infection and competitively excludes all other virus(More)
There are many biological steps between viral infection of CD4(+) T cells and the production of HIV-1 virions. Here we incorporate an eclipse phase, representing the stage in which infected T cells have not started to produce new virus, into a simple HIV-1 model. Model calculations suggest that the quicker infected T cells progress from the eclipse stage to(More)
We explore how an infected cell's virion production rate can affect the relative fitness of a virus within a host. We perform an invasion analysis, based on an age-structured model of viral dynamics, to derive the within-host relative viral fitness. We find that for chronic infections, in the absence of trade-offs between viral life history stages, natural(More)
Filamentous fungi are ubiquitous and ecologically important organisms with rich and varied life histories, however, there is no consensus on how to identify or measure their fitness. In the first part of this study we adapt a general epidemiological model to identify the appropriate fitness metric for a saprophytic filamentous fungus. We find that fungal(More)
We present moments and likelihood methods that estimate a DNA substitution rate from a group of closely related sister species pairs separated at an assumed time, and we test these methods with simulations. The methods also estimate ancestral population size and can test whether there is a significant difference among the ancestral population sizes of the(More)
Upstream open reading frames (uORFs) are protein coding elements in the 5' leader of messenger RNAs. uORFs generally inhibit translation of the main ORF because ribosomes that perform translation elongation suffer either permanent or conditional loss of reinitiation competence. After conditional loss, reinitiation competence may be regained by, at the(More)