We are seeking a highly motivated researcher to fill a three-year position involving comprehensive characterization of the autophagic process that selectively traffics intra-cellular cholesterol, using state-of-the-art bioimaging and proteomics. The successful applicant will mainly work in the group of Associate Professor Jonathan Brewer, in close collaboration with Professor Martin Røssel Larsen, at the University of Southern Denmark (Odense). Additionally, they will be an integral part of an interdisciplinary team led by the Kim Rewitz lab at the University of Copenhagen.

The position is to commence 1 September 2023, or as soon as possible thereafter. Application deadline: 15 August 2023.

The chosen candidate will work in a dynamic and international environment, based at the Department Biochemistry and Molecular Biology, Faculty of Science, University of Southern Denmark. They will have access to state-of-the-art equipment for bioimaging and proteomics in the groups of Jonathan Brewer and Martin Røssel Larsen, providing invaluable support for the project and the opportunity to develop essential skills for future work.

Project background
Sterols, such as cholesterol, are important for the structure and stability of cell membranes, and they also play a role in the development of animals. However, modern lifestyles, including high-cholesterol diets, can disrupt the balance between sterols and lipids in cells, which can contribute to diseases like atherosclerosis and certain cancers. Current treatments for high cholesterol are limited to statin drugs, which only prevent further cholesterol accumulation. The Rewitz lab (University of Copenhagen) recently identified an autophagic process that can selectively remove intra-cellular cholesterol buildup, and manipulating certain regulators can promote its clearance. However, the mechanisms behind this process are not yet fully understood, and there are few tools available for visualizing or measuring intra-cellular cholesterol levels.

The Novo Nordisk Foundation has awarded our team three years of funding to explore various areas related to cholesterol trafficking using the fruit fly Drosophila as a model system. The candidate for the present position will work on the biochemical and imaging aspects of the project together with a candidate at the University of Copenhagen who will develop different Drosophila based models including in vivo proximity-labelling and pull-down experiments using tagged GRASP, Rab, and other relevant proteins.

This project aims to identify the mechanisms by which intra-cellular cholesterol is recognized and targeted for auto-phagosomal removal, using an integrative approach combining genetics with proteomics and super-resolution imaging. With the long-term goal of developing strategies to prevent disease progression by reducing intra-cellular cholesterol accumulation.

Job description
The successful candidate will pursue novel in vivo imaging techniques using advanced bioimaging techniques including confocal, stimulated emission depletion (STED) and MINFLUX microscopy as well as Raman-based methods, to develop approaches for the monitoring and measurement of intra-cellular cholesterol and its trafficking, both under normal conditions and with genetic manipulations. Cholesterol bearing Raman-active isotopic and alkyne labels will be prepared, and the function of these labelled species in vivo will be monitored using Coherent Stokes Anti-Raman (“CARS”) and Stimulated Raman Scattering imaging. Intra-cellular cholesterol levels will also be monitored using genetically encoded fluorescent sterol-binding probes. The candidate will also be responsible for preforming proteomics and PTMomics assay to characterize the various mutants and identify targets for further genetic manipulations.

Your qualifications
We are looking for a highly motivated and enthusiastic scientist with the following competencies and experience:

Essential experience and skills:

• A PhD in molecular biology, biophysics, nanotechnology, physics, biochemistry, or similar field.
• Motivation and interest to work with an interdisciplinary project.
• Experience with bioimaging and / or proteomics.
• Proficient communication skills and the ability and desire to work as part of a team.
• Excellent English skills, both written and spoken.

Desirable experience and skills:

• Experience with bioimaging and preparation of biological samples for microscopy.
• Experience with super resolution optical microscopy such as STED, MINFLUX or STORM.
• Experience with Raman based imaging such as Coherent Stokes Anti-Raman (CARS) and / or Stimulated Raman Scattering imaging (SRS).
• Experience with LC-MSMS based proteomics and PTMomics.

Questions
For further information please contact Associate Professor Jonathan R. Brewer, e-mail: [email protected].

Application, salary etc.
The successful applicant will be employed in accordance with the agreement between the Ministry of Finance and AC (the Danish Confederation of Professional Associations). Please check links for more information on salary and taxation.

The application must include the following:
• A curriculum vitae including information on previous employment.
• A full list of publications stating the scientific publications on which the applicant wishes to rely.
• Motivated letter of application (max. one page).
• a) PhD certificate and b) Master of Science certificate. If the PhD has not been completed, a written statement from the supervisor will do.

Shortlisting may be used in the assessment process.

Incomplete applications and applications received after the deadline will neither be considered nor evaluated.

To qualify you must have passed a PhD or equivalent. Applications will be assessed by an expert assessor/committee. Applicants will be informed of their assessment by the university.

The University wishes our staff to reflect the diversity of society and thus welcomes applications from all qualified candidates regardless of personal background.

Applications must be submitted electronically using the link "Apply online". Attached files must be in Adobe PDF or Word format. Each box can only contain a single file of max. 10 Mb. We strongly recommend that you read How to apply before you apply.

Further information for international applicants about entering and working in Denmark.