The Department of Physics, Chemistry and Pharmacy at the University of Southern Denmark invites applications for a position as postdoc in the ABC transporter area.

The Department of Physics, Chemistry and Pharmacy is one of four departments at the Faculty of Science, SDU and is located in Odense. The Department of Physics, Chemistry and Pharmacy is a department focused on basic research. We are happy to move beyond traditional disciplines and work to develop new technologies and sciences across physics, chemistry, pharmacy, mathematics, computer science and biology. The department’s research thus contributes to new knowledge and solutions with applications in the areas of climate, environment, energy and health.

The department handles research in chemistry, physics and pharmacy along with several interdisciplinary areas, and also houses several major research centres. The Department of Physics, Chemistry and Pharmacy is responsible for the educations in chemistry, medicinal chemistry and physics, as well as the bachelor education in pharmacy.

The postdoc position is placed in the Section for Chemistry and Pharmacy and the chosen candidate will work in a highly collaborative atmosphere with theorists and experimental scientists.

Project:
The overall aim of the project is to investigate if the ATP-binding site of the human Permeability protein 170 (P-gp), which is a protein known to be part of the multidrug resistance problem in cancer and to limit the oral bioavailability of drug substances, is drugable. The ATP binding site is highly conserved among ATP-binding cassette transporters (ABC transporters).

The current state is that a number of compounds have been predicted to interact with the ATP-binding site of P-gp, the protein product for ABCB1 based on computational procedures. The compounds selected have been investigated in vitro for their interaction with human P-gp in two different assays:
1) An intact cell-based (MDCK 1 MDR1 cells) assay using calcein-AM as a probe. This assay reveals if the test compound inhibits the P-gp mediated transport.
2) A vesicle-based assay using inside-out Sf9 vesicles expressing human P-gp. This assay is also an inhibition assay investigating if a test compound is able to decrease the ATP-consumption induced by substrate transport. The compounds investigated so far have affinities comparable to the affinity of ATP itself.

The following tasks are required by the postdoc

Operational tasks:
Investigate compounds selected from the computational work using the calcein-AM and ATP assays along with investigating if the compounds induce cellular toxicity.

Development tasks:
The following should be investigated:
a) Establish procedures in-house to isolate and validate inside-out vesicles for relevant ABC transporters, starting with P-gp.
b) Establish new procedures to assess compound binding to P-gp. This could be based on a) Isothermal microcalorimetry and/or b) Cell-based assays allowing for real-time monitoring of conformational changes in P-gp by Förster resonance energy transfer (FRET) or Luminescence Resonance Energy Transfer (LRET).
c) If the selected compounds show nano- to lower micro-molar affinity for P-gp, the specificity and selectivity needs to be addressed by looking at binding to other ABC transporters such as e.g. BCRP and MRP2, and therefore vesicles mentioned under a) with accompanying methods should be established.

The postdoc's duties will include research as well as teaching.

We are looking for a colleague who is:

• A PhD in pharmacy, cell biology, chemistry, biomedical sciences, molecular biology, or a related field.
• Experienced in cell culturing and bioassays.
• Experienced in working with drug substances with solubility and stability issues.
• Experienced with ABC transporters or solute carrier and their interaction with drug substances.
• Experienced in In Vitro assays looking at drug diffusion or binding.
• Organized and detail oriented.
• Excellent in English.
• Social and a collaborator.

Duration: One year starting no later than 1 September 2023, with the possibility of one year extension.

Contact: Professor Carsten Uhd Nielsen at [email protected].

Deadline: 15 June 2023.

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.

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.