Researcher, structure-function studies of amyloid and secondary nucleation - Hiring in process/Finished, not possible to apply

The Department of Cell and Molecular Biology is organized into seven research programmes which all focus on different areas of cell and molecular biology: Computational Biology and Bioinformatics, Microbiology and Immunology, Molecular Biology, Molecular Biophysics, Molecular Evolution, Molecular Systems Biology and Structural Biology. The scientific basis of what we do lies in biology, but our research overlaps with other areas such as medicine, computer science, mathematics, chemistry, engineering sciences and physics. In total, we are over 200 staff and ~60 Ph.D. students. Please read more about the department’s work at https://icm.uu.se.

The advertised position is within the Structural Biology program (http://www.icm.uu.se/strukturbiologi). The researcher will work in an innovative, challenging and exciting project led by Stefan Knight, where interactions between BRICHOS domains and systematically designed proteins will be studied using X-ray crystallography, directed mutagenesis and complementary techniques to understand how BRICHOS domains inhibit amyloid formation. The employee will work in an international and dynamic environment. We have a well-equipped lab, good access to synchrotron beam time for collecting X-ray diffraction data, and access to a local cryo-EM facility and a national cryo-EM facility in Stockholm. For more information about the research group, see https://www.icm.uu.se/structural-biology/knight-lab/.

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Duties
We are looking for an experienced researcher with excellent credentials and strong motivation to work on scientific problems, and who is not afraid to take on a challenging high-risk project with great potential. The employee will work in a VR-funded project aimed at understanding medically relevant aspects of Ab amyloid formation, focusing on how the surface of Ab fibrils catalyses secondary nucleation (and thereby formation of toxic amyloid intermediates), and on how BRICHOS domains inhibit this process. To get around the significant technical problems that limit structural and mechanistic studies of amyloid fibrils, the project is based on a novel generic concept for the design of small soluble proteins that mimic amyloid fibrils ('single chain recombinant amyloid-mimicking proteins', SCRAPs).

Duties include data-based computer-assisted design and further development of SCRAP constructs, cloning, expression and purification of SCRAPs and BRICHOS domains, characterization with biochemical and biophysical methods, binding studies, structure determination of BRICHOS domains and BRICHOS:SCRAP complexes, mainly with X-ray crystallographic methodology, as well as directed mutagenesis to test structure-based hypotheses. Structural studies with cryo-electron microscopy of BRICHOS domains bound to amyloid fibrils may also be included. The researcher is expected to actively participate in all aspects of the research process, from detailed experimental design and strategy to evaluation, analysis, and synthesis of results.

The researcher will work in close collaboration with the research leader. The project will include collaboration with Anna Sundborger-Lunna's (https://www.icm.uu.se/structural-biology/sundborger-lunna-lab/) and Jan Johansson's (https://staff.ki.se/people/janne-johansson) research groups. A strong track record with documented relevant laboratory skills, motivation, good collaboration skills, and good ability to prioritize and work towards defined goals within given time frames is a prerequisite for the position.

Requirements
PhD degree in structural biology, biochemistry, biophysics or a related field, or a foreign degree deemed to be equivalent to a PhD in these subjects. Only applicants with considerable (minimum three years) postdoc or equivalent research experience will be considered for employment.

• Documented experience of independent work with proteins, including cloning, expression and purification as well as characterization and quality control of recombinant proteins
•  Documented experience in structural biology and/or biophysical methods
• Documented scientific proficiency, demonstrated in scientific publications and presentations at national and international conferences
• Excellent spoken and written English
• Good cooperation skills

Additional qualifications
Documented experience with directed mutagenesis as well as with biophysical methods to study binding (e.g. thermofluor, ITC, SPR, microscale thermophoresis) is desirable and meritorious. Experience with programming (especially Python and/or Perl) and/or structural bioinformatics is also meritorious.

The application should include:·        

• Cover letter 
• PhD degree certificate
• CV including publication list
• Contact information for three reference persons

About the employment
The employment is a permanent position, probationary period may be applied. Scope of employment 100%. Starting date May 1 or as agreed. Placement: Uppsala. 

For further information about the position, please contact: Stefan Knight, tel. 018-471 4554, stefan.knight@icm.uu.se.

Please submit your application by 31 of March 2023, UFV-PA 2023/1005

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