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Developing fungal bromodomain inhibitors as a potential new class of antifungal drugs

ABG-100175 Thesis topic
2021-09-20 Public/private mixed funding
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Institut de Biologie Structurale
Grenoble - Auvergne-Rhône-Alpes - France
Developing fungal bromodomain inhibitors as a potential new class of antifungal drugs
  • Biology
  • Biochemistry
  • Chemistry
protein biochemistry, X-ray crystallography, drug discovery, epigenetics

Topic description

Background. Invasive fungal infections are a major global health concern, causing over a million deaths per year.  Because of the limited number of antifungal drugs and the emergence of drug-resistant strains there is an urgent need to develop new therapeutic strategies. Candida species such as C. albicans and C. glabrata are among the most significant human fungal pathogens, with invasive candidiasis yielding 30-40% mortality. We recently identified an epigenetic reader domain, the bromodomain from the fungal transcription factor Bdf1, as a potential new target for antifungal therapy (Mietton et al., Nature Comm.2017, 8:15482), opening up new possibilities for developing epigenetic drugs to combat fungal infection. 

Objectives. The objectives of this project are to further validate the inhibition of Bdf1 bromodomains as an antifungal strategy in Candida species and to develop small-molecule inhibitors for translation into a new class of antifungal drug.The project is a collaboration of four partner labs with complementary expertise in fungal genetics and epigenetics, biochemistry, medicinal chemistry and structural biology.

Responsibilities. The PhD student will employ a wide range of techniques that include protein expression and purification, biochemical/biophysical and cell-based assays and structure determination by X-ray crystallography. 

Funding category

Public/private mixed funding

Funding further details

Presentation of host institution and host laboratory

Institut de Biologie Structurale

Research at the Institut de Biologie Structurale (IBS) aims to understand the molecular mechanisms underlying cellular processes and human disease. Its 270 researchers and staff (including 30 PhD students) are organized into 20 groups that perform interdisciplinary research at the interface of biology, physics and chemistry. Located on the European Photon and Neutron (EPN) Campus in Grenoble, France (http://www.epn-campus.eu), the IBS is a member of the Partnership for Structural Biology (http://www.psb-grenoble.eu), which provides cutting edge facilities for innovative research in the biomolecular sciences, including on-site access to synchrotron and cryo-EM facilities. 

The IBS is affiliated with the Doctoral School of Chemistry and Life Sciences at the University of Grenoble Alpes.

 

Host laboratory: https://www.ibs.fr/research/research-groups/epigenetics-and-molecular-pathways-group-c-petosa/petosa-team/ 

PhD title

Doctorat de Chimie et Sciences du Vivant

Country where you obtained your PhD

France

Institution awarding doctoral degree

Université Grenoble Alpes

Graduate school

Chimie et Sciences du Vivant

Candidate's profile

Highly motivated students with a background in chemistry, biology or other life sciences and a strong interest in structural biology or drug discovery are encouraged to apply. Candidates should have a Master’s Degree (or equivalent) or should expect to receive their degree in the near future. Laboratory experience in biochemistry or molecular biology is an advantage.

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