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Development of tools for the analysis of molecular clock and their application for a case of Hepatitis C Virus epidemics with known infection history

Objective

The strategic directions of multidisciplinary research at the Institute of Oceanology of the Polish Academy of Sciences include genetics and molecular biology of marine organisms, fields of research where progress increasingly depends on expertise in computational biology. This project will allow making the first step in introducing this much-needed expertise in the Institute and indeed in the region, which we hope will benefit several projects at the Institute (molecular systematics of marine invertebrate s, population genetics of fish and molluscs, marine microbiology). However, considering the short timeline, the utility of tools developed during the project will first be tested on a dataset of Hepatitis C Virus sequences obtained from an epidemic with kn own infection history. These data allow constructing a true phylogenetic tree with extensive temporal information, as the times for both the external nodes and crucial internal nodes are known. HCV displays one the highest rates of evolution detected in an y life form (reaching 10-2 substitutions/site/year. Moreover, extreme heterogeneity of substitution rate is observed in some of the regions of HCV genome. The project will concentrate on resolving the following issues:
(1) the level of heterogeneity of the rate of substitution among sites,
(2) the use of complex models (for example, models which allow multiple substitution matrices) for possibly better description of the data,
(3) the effects of the presence of positive selection on the molecular clock,
(4) the nature of amino acid substitutions that occur, especially in the context of the quasispecies hypothesis and the possibility of multiple infections. By analysing sequences coming from a major human pathogen, we hope to provide insight into the molecular biology of HCV and other RNA viruses, relevant not only for molecular evolution, but also for molecular medicine, molecular epidemiology and forensics.

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Coordinator

INSTITUTE OF OCEANOLOGY, POLISH ACADEMY OF SCIENCES

Address

Ul. Powstancow Warszawy 55
Sopot

Poland

Project information

Grant agreement ID: 6328

  • Start date

    1 June 2005

  • End date

    31 May 2006

Funded under:

FP6-MOBILITY

Coordinated by:

INSTITUTE OF OCEANOLOGY, POLISH ACADEMY OF SCIENCES

Poland