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Millions of people living with HIV receive the Integrase inhibitor Dolutegravir as recommended by the WHO. This drug combines very high efficacy in clinical trials with a difficult track towards viral failure by acquisition of drug-resistance mutations. In this project, Dolutegravir resistance is studied, with a focus on mutations that can be expected in the targeted Integrase enzyme, but also unexpected mutations elsewhere in the HIV genome. In particular, changes in regulatory HIV sequences have recently been reported to contribute to Dolutegravir-resistance (see e.g. Das AT & Berkhout B. How polypurine tract changes in the HIV-1 RNA genome can cause resistance against the Integrase inhibitor Dolutegravir. MBio. 2018 Apr 10;9(2). pii: e00006-18).
The molecular mechanism underlying this novel resistance pattern will be analyzed in the laboratory (BSL-3) by means of novel virus evolution and powerful molecular biology techniques. This PhD project is part of a new international consortium funded by the National Institutes of Health (NIH, USA) and includes other teams from Erasmus MC, Harvard Medical School, University of Liverpool and University of São Paulo.
We are looking for a bright and motivated PhD student candidate with a recently obtained (or soon to be received) Master’s degree in biological, biochemical or biomedical sciences (or comparable studies) with laboratory experience in molecular biology and a research interest in virology and virus evolution.
Fixed-term contract: 48 months.
We offer you ample opportunity for development, deepening and broadening, additional training and a place to grow! Working at AMR means working in an inspiring and professional environment where development is encouraged in every respect.
For an overview of all our other terms of employment, see https://werkenbijamc.nl/arbeidsvoorwaarden-amr/.
At the Laboratory of Experimental Virology (Department of Medical Microbiology, AMC), both basic and applied HIV research is performed. Basic research focuses on several steps in the viral replication cycle, such as regulation of viral gene expression and HIV RNA processing. Applied research focuses on the development of an HIV vaccine and novel strategies to inhibit HIV replication. We have a long-standing interest in studying the action of novel drugs and drug-resistance mechanisms. Basic and applied research are not separated, but intermingled to complement each other.
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