Doctoral position in activation mechanisms of Frizzleds

Do you want to contribute to top quality medical research?

To be a doctoral student means to devote oneself to a research project under supervision of experienced researchers and following an individual study plan. For a doctoral degree, the equivalent of four years of full-time doctoral education is required.

The research group

In the division Receptor Biology & Signaling headed by Prof Gunnar Schulte, G protein-coupled receptors (GPCRs) and particularly Class F receptors are in focus. The work aims to better understand how ligands interact with Class F receptors, how conformational changes are established to activate the receptors and – consequently – how those initiate interaction and selective activation of intracellular signaling components. Class F receptor structure and functional selectivity of Class F receptors towards heterotrimeric G proteins or other pathways are analyzed with the hope to exploit the novel knowledge therapeutically.

For recent publications please see:

1. Scharf MM, Kinsolving J#, Grätz L#, Voss JH, Carrasco-Busturia D, Forsberg B, Kolb P, Schulte G¤. In silico docking yields small molecule compounds targeting the core of Frizzled 7 as negative allosteric modulators. Nature Communications. 2025 in press.
2. Bous J¤, Kinsolving J, Grätz L, Scharf MM, Voss JH, Selcuk B, Adebali O, Schulte G¤. Structural basis of Frizzled 7 activation and allosteric regulation. Nature Communications. 2024 Aug 28;15(1):7422. https://www.nature.com/articles/s41467-024-51664-4 PMID: 39198452.
3. Grätz L#, Kowalski-Jahn M#, Scharf MM, Kozielewicz P, Jahn M, Bous J, Lambert NA, Gloriam DE, Schulte G. Pathway selectivity in Frizzleds is achieved by conserved micro-switches defining pathway-determining, active conformations. Nature Communications. (2023);14(1):4573. https://www.nature.com/articles/s41467-023-40213-0 PMID: 37516754.
4. Kowalski-Jahn M#, Schihada H#, Turku A, Huber T, Sakmar TP, Schulte G¤. Frizzled BRET sensors based on bioorthogonal labeling of unnatural amino acids reveal WNT-induced dynamics of the cysteine-rich domain. Science Advances. 2021; 7(46):eabj7917. DOI: 10.1126/sciadv.abj79 PMID: 34757789.
5. International Union of Basic and Clinical Pharmacology. CXV: The Class F of G Protein-Coupled Receptors. Schulte G. Pharmacological Reviews. 2024:PHARMREV-INR-2023-001062. https://doi.org/10.1124/pharmrev.124.001062. PMID: 38955509

The doctoral student project and the duties of the doctoral student

The doctoral project is aimed to better understand the molecular underpinnings of Frizzled activation both on a structural and functional level. Furthermore, we aim to understand how mutations in FZD4 that are causally linked to an inherited eye disease (familial exudative vitreoretinopathy or short FEVR) impact receptor behavior. The work is embedded in the current activities of the group with the breadth of methodology characteristic for the laboratory ranging from in silico approaches (protein modelling, docking, MD simulations), molecular biology (cloning, mutagenesis), biophysical methodology (BRET), receptor pharmacology, protein chemistry and structural biology (CryoEM). In parallel to the research education in the group as well as in collaboration with national and international collaborators, the doctoral student will be involved in laboratory and administrative duties as well as undergraduate teaching. Furthermore, opportunities for hands-on Masters student supervision will be available.

What do we offer?

A creative and inspiring environment full of expertise and curiosity. Karolinska Institutet is one of the world's leading medical universities. Our vision is to pursue the development of knowledge about life and to promote a better health for all. At Karolinska Institutet, we conduct successful medical research and hold the largest range of medical education in Sweden. As a doctoral student you are offered an individual research project, a well-educated supervisor, a vast range of elective courses and the opportunity to work in a leading research group. Karolinska Institutet collaborates with prominent universities from all around the world, which ensures opportunities for international exchanges. You will be employed on a doctoral studentship which means that you receive a contractual salary. Employees also have access to our modern gym for free and receive reimbursements for medical care.

Eligibility requirements for doctoral education

In order to participate in the selection for a doctoral position, you must meet the following general (A) and specific (B) eligibility requirements at latest by the application deadline.

It is your responsibility to certify eligibility by following the instructions on the web page Entry requirements (eligibility) for doctoral education.

A) General eligibility requirement

You meet the general eligibility requirement for doctoral/third-cycle/PhD education if you:

1. have been awarded a second-cycle/advanced/master qualification (i.e. master degree), or
2. have satisfied the requirements for courses comprising at least 240 credits of which at least 60 credits were awarded in the advanced/second-cycle/master level, or
3. have acquired substantially equivalent knowledge in some other way in Sweden or abroad.*

Follow the instructions on the web page Entry requirements (eligibility) for doctoral education.

*If you claim equivalent knowledge, follow the instructions on the web page Assessing equivalent knowledge for general eligibility for doctoral education.

B) Specific eligibility requirement

You meet the specific eligibility requirement for doctoral/third-cycle/PhD education if you:

- Show proficiency in English equivalent to the course English B/English 6 at Swedish upper secondary school.

Follow the instructions on the web page English language requirements for doctoral education.

Verification of your documents Karolinska Institutet checks the authenticity of your documents. Karolinska Institutet reserves the right to revoke admission if supporting documents are discovered to be fraudulent. Submission of false documents is a violation of Swedish law and is considered grounds for legal action.

(A) and (B) can only be certified by the documentation requirement for doctoral education.

Skills and personal qualities

The candidate should have a theoretical and practical background in biochemistry, biomedicine, molecular biology, pharmacology, or structural biology (experience with transmembrane proteins, GPCRs and CryoEM would be advantageous). We expect a successful applicant to have basic knowledge in GPCR pharmacology and plate reader-based assays (e g BRET or FRET or luciferase assays) and it would be desirable if experience in molecular biology and in silico approaches exists. It is necessary for the motivated student to thrive in an interdisciplinary environment and a dynamic and international research team. It is required that the student has extensive practical lab experience exemplified by successful Bachelor or Masters projects or other e. g. extracurricular laboratory activities.

Terms and conditions

The doctoral student will be employed on a doctoral studentship maximum 4 years full-time.

Application process

Submit your application and supporting documents through the Varbi recruitment system. Use the button in the top right corner and follow the instructions. We prefer that your application is written in English, but you can also apply in Swedish.

Your application must contain the following documents:

- A personal letter and a curriculum vitae
- Degree projects and previous publications, if any
- Any other documentation showing the desirable skills and personal qualities described above
- Documents certifying your general eligibility (see A above)
- Documents certifying your specific eligibility (see B above)

Selection

A selection will be made among eligible applicants on the basis of the ability to benefit from doctoral education. The qualifications of the applicants will be evaluated on an overall basis.

Karolinska Institutet uses the following bases of assessment:

- Documented subject knowledge of relevance to the area of research
- Analytical skill
- Other documented knowledge or experience that may be relevant to doctoral studies in the subject.

All applicants will be informed when the recruitment is completed.

https://ki.se/en/research/research-areas-centres-and-networks/research-groups/receptor-biology-and-signaling-schulte-lab

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