Elucidating the structure and function of parasite mitochondrial cardiolipin synthases

Website Aarhus University

Last Day to Apply: 1 August 2024

Project description:
All eukaryotic organisms rely on cell organelles called mitochondria for their function and survival as many critically important processes are centered on mitochondria. Famous amongst these processes is the production of cellular energy in the form of ATP from aerobic respiration reactions of electron transport chains and oxidative phosphorylation. The membrane protein complexes responsible for electron transport and oxidative phosphorylation reside in the mitochondrial inner membrane where their stability and integrity depend critically on the presence of a unique phospholipid known as cardiolipin.

Cardiolipin (CL) is essentially a dimeric glycerophospholipid with a small hydrophilic head group of a bridging glycerol moiety and a bulky hydrophobic part of four acyl chains. This gives CL an overall conical shape which causes induction of membrane curvature, a hallmark morphology of mitochondrial inner membranes.

Normally, mitochondria synthesize cardiolipin in a process different from bacterial pathways, however, in mitochondria of the human parasites Trypanosoma brucei and Toxoplasma gondii, bacterial-like cardiolipin synthases have been retained throughout evolution. Therefore, these proteins are interesting targets for developing new anti-parasite drugs to combat infections.

In this three-year PhD project, we will investigate cardiolipin synthases from T. brucei and T. gondii to understand their structure and function. Furthermore, we will study native mitochondrial interactions partners of the enzymes to understand their interactome and possible higher-order complexes in mitochondrial inner membranes. The project will use molecular biology and protein biochemistry methods to study isolated enzymes expressed and purified from bacteria. Activity assays will make use of colorimetric signal amplification of cardiolipin synthesis and protein structures will be determined using cryo-electron microscopy and single particle analysis. For interactome studies, we will collaborate with international partners for obtaining native parasite mitochondria as source material for purifying intact cardiolipin synthase complexes. These complexes will be analyzed with mass spectrometry (in-house facility) as well as structural studies using cryo-EM.

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Qualifications and specific competences:
Applicants must have a relevant Master’s degree or at least one year of a Master’s degree in molecular biology/protein biochemistry. Applicants must also have good communications skills in English (oral and written).
Place of employment and place of work:
The place of employment is Aarhus University, and the place of work is Molecular Biology and Genetics, Universitetsbyen 81, 8000 Aarhus C, Denmark.

Contacts:
Applicants seeking further information for this project are invited to contact: Assistant professor, Rasmus Kock Flygaard, rkf@mbg.au.dk or Professor Esben Lorentzen el@mbg.au.dk

How to apply:
For information about application requirements and mandatory attachments, please see the application guide Please read the Application guide thoroughly before applying.
When ready to apply, go to https://phd.nat.au.dk/for-applicants/apply-here/  (Note, the online application system opens 1 June 2024)
1. Choose August 2024 Call with deadline 1 August 2024 at 23:59 CEST.
2. You will be directed to the call and must choose the programme “Molecular Biology and Genetics”.
3. In the boxed named “Study”: In the dropdown menu, please choose: “Elucidating the structure and function of parasite mitochondrial cardiolipin synthases (Esfpmc)”

Please note:
The programme committee may request further information or invite the applicant to attend an interview.
At the Faculty of Natural Science at Aarhus University, we strive to support our scientific staff in their career development. We focus on competency development and career clarification and want to make your opportunities transparent. On https://nat.au.dk/en/about-the-faculty/career you can find information on all types of scientific positions, as well as the entry criteria we use when assessing candidates. You can also read more about how we can assist you in your career planning and development.

Group Leader
Rasmus Kock Flygaard

To apply for this job please visit phd.nat.au.dk.

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