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Development of novel strategies for HIV treatment and cure
Belgium (BeMSA) - KU Leuven, Leuven
Molecular Virology and Gene Therapy
Prof.dr. Zeger Debeyser
Type of Research Project
- Basic science
What is the background of the project?
Infection with the human immunodeficiency virus type 1 (HIV-1) remains a substantial global public health problem. Although a combination of antiretroviral therapy (cART) effectively suppresses HIV replication and profoundly increases the survival of patients, a definitive cure is not achievable yet. Interruption of cART typically results in a rebound of virus replication. This is primarily due to the fact that HIV ingeniously escapes from the continuous immune surveillance in reservoirs of latently infected cells that are not susceptible to drug therapy. Moreover, a rapid replication rate, an extensive genetic diversity and suboptimal adherence to treatment sustain the emergence of drug-resistant viral strains resulting in treatment failure. Therefore, there is a continuous demand for a novel and better antiretrovirals to control the HIV pandemic with the hope to eventually achieve permanent remission of the disease. We identified and characterized LEDGF/p75 (Lens Epithelium Derived Growth Factor) as a cellular protein that tethers HIV integration into gene bodies, and more recently Bromo- and Extra-Terminal domain (BET) proteins as tethers for Murine Leukemia Virus (MLV). (De Rijck et al., Cell Reports, 2013).
What is the aim of the project?
(pre)clinical development of LEDGINs which are inhibitors of the interaction between integrase and LEDGF/p75 as proven by our research group in 2010 (Christ et al., Nat Chem Biol, 2010).
What techniques and methods are used?
Molecular biology (cloning, sequencing, Real-Time Quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR), etc.), cell culture, retroviral integration-site analysis, bioinformatics, biochemistry (Western blotting, Enzyme-Linked Immuno Sorbent Assay, luciferase assay, etc.), viral-vector technology, cell biology, and confocal microscopy.
What is the role of the student?
- The student will mainly observe
- The student will observe the practical experiments but will be highly involved in the analysis of the results
- The tasks will be done under supervision
What are the tasks expected to be accomplished by the student?
The student will follow along with the research activities of a Ph.D. student. Mini meetings and official lab meetings will be followed by the student. We also ask the student to read literature since this will help the understanding of the topic. The student should also be motivated and ask questions to be able to learn in an active way. All of the techniques mentioned in this form will be demonstrated to the student. If the student understands the techniques well, he/she might be able to help a Ph.D. student with the technical aspects.
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
What is expected from the student at the end of the research exchange? What will be the general outcome of the student?
- No specific outcome is expected
What skills are required of the student? Is there any special knowledge or a certain level of studies needed?
Are there any legal limitations in the student’s involvement
Students are not allowed to handle infectious HIV due to safety concerns.
Type of students accepted
This project accepts:
- Debyser Z; Christ F; De Rijck J; Gijsbers R (2015) Host factors of retroviral integration site selection. Trends Biochem Sci 40; 108-116
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