PhD fellowship in Medicinal Chemistry Department of Drug Design and Pharmacology

PhD fellowship in Medicinal Chemistry

Department of Drug Design and Pharmacology
Faculty of Health and Medical Sciences (HEALTH/SUND)

University of Copenhagen

Within the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No 860517, University of Copenhagen is offering one PhD position for an Early Stage Researchers (ESR), commencing 31 December 2021 or as soon as possible hereafter. The position is 36 months and is funded partially by the Horizon 2020 grant and partially by Department of Drug Design and Pharmacology and the Novo Nordisk Foundation Center for Protein Research at University of Copenhagen.

The UBIMOTIF consortium includes 13 research groups and 6 partners from 10 European countries and is a joint training and research program with focus on discovery, characterization and exploitation of short linear motifs in the ubiquitin system.

Visit www.ubimotif.ku.dk for more information.

Project description

The successful applicant will join the multidisciplinary EU-funded Marie Sklodowska Curie International PhD training network UBIMOTIF aiming to understand the role of short linear motifs (SLiMs) in the regulation of ubiquitin signaling with a focus on DNA repair and mitotic regulation.

The aim of the current PhD project is to develop new small-molecule inhibitors and degraders of Cullin 3 (Cul3) adaptor proteins by using fragment-based drug discovery (FBDD) and proteolysis targeting chimeras (PROTACs) strategies. A particular focus will be on kelch domain-containing adaptor proteins.

The main tasks of the PhD student will be to design and synthesize new analogues of small-molecule inhibitors to optimize them for affinity, selectivity, and cell activity. The design is carried out by structure-based drug design using available X-ray crystal structures of ligands and fragments binding to the target and molecular docking to evaluate design ideas. Compounds will be made by the student using synthetic organic chemistry and characterized by relevant analytical techniques. The student will also explore prodrug strategies and convert the most interesting lead compounds into PROTACs for targeted protein degradation. To evaluate the affinity and activity of the compounds, the PhD student will apply various assays based on e.g. fluorescence polarization and surface plasmon resonance as well as cell-based assays. As part of the UBIMOTIF training network, two secondments of 3 months each are scheduled. Here, the student will visit collaborating groups at University of Copenhagen and in Uppsala, Sweden, respectively, to test for selectivity, cell activity, and to design and synthesize PROTACs.

Principal supervisor
Associate Professor Anders Bach, Department of Drug Design and Pharmacology
E-mail:  [email protected] , direct phone: +45 2128 8604.

Profile: https://drug.ku.dk/disciplines/medicinal-chemistry/bach-group/

Our group and research

The applicant will become part of Bach Group, which includes postdocs, PhD students, and master students. We use FBDD on disease-relevant protein-protein interactions in order to evaluate the druggability of selected targets and identify novel chemical probes and therapeutic principles. We do fragment screening using biochemical and sensitive biophysical methods, and optimize the hits by medicinal chemistry, X-ray crystallography, and pharmacological assays. The targets we focus on are involved in oxidative stress and inflammation, and they play crucial roles in numerous diseases and pathological processes. Examples are Keap1, which regulates the endogenous antioxidant response, and the superoxide-generating multi-subunit enzyme complex NADPH oxidase 2 (NOX2).

We emphasize the importance of interdisciplinarity, teamwork, openness, and knowledge- and information sharing in our work together. We have group meetings, journal clubs, and departmental seminars.

Our department

The Department of Drug Design and Pharmacology (www.drug.ku.dk) delivers drug-related research and research-based teaching within a wide range of drug-related disciplines, spanning the molecular, cellular, and pharmacological levels.

Information about the Department can be found at https://drug.ku.dk/

Job description
Your key tasks as a PhD fellow at the Faculty of Health and Medical Sciences are to:

• Carry through an independent research project under supervision
• Complete PhD courses or other equivalent education corresponding to approx. 30 ECTS points
• Participate in active research environments including two secondments at other research institution in Copenhagen and Uppsala
• Obtain experience with teaching and other types of dissemination related to your PhD project
• Participate in the undergraduate teaching of students in pharmaceutical sciences
• Participate in national and international conferences and scientific meetings
• Write a PhD thesis on the grounds of your research project

Required qualifications
As an applicant you must have:

• qualifications corresponding to a master’s degree in chemistry, medicinal chemistry, pharmaceutical chemistry, pharmacy, chemical engineering or related areas prior to the starting date
• Fluency in English and excellent communication skills

Applicants will also be required to meet the Marie Skłodowska-Curie Early Stage Researcher eligibility criteria:

• Mobility Rule - Researchers must not have resided or carried out their main activity (work, studies, etc.) in Denmark for more than 12 months in the 3 years immediately before the recruitment date. Compulsory national service, short stays such as holidays, and time spent as part of a procedure for obtaining refugee status are not taken into account.
• Early Stage Researcher (ESR) criteria - ESRs must, at the date of recruitment by the host organisation, be in the first four years (full-time equivalent research experience) of their research careers and have not been awarded a doctoral degree. Full-Time Equivalent Research Experience is measured from the date when the researcher obtained the degree entitling him/her to embark on a doctorate (either in the country in which the degree was obtained or in the country in which the researcher is recruited, even if a doctorate was never started or envisaged).

Please note that you will only be considered for the position if you fulfill the eligibility criteria.

Preferred qualifications
We are looking for a highly motivated, enthusiastic, and science-minded person with competencies and experience related to:

• Synthetic organic chemistry of small-molecules in relation to drug discovery.
• Purification and characterization of small-molecules by standard analytical methods (e.g. NMR, LCMS).
• Design of small-molecule analogues by structure-based drug design using X-ray crystallographic data and molecular docking.
• Medicinal chemistry concepts like structure-activity relationship (SAR), physicochemical properties related to drug-likeness and biological activity, FBDD, prodrugs, and PROTACs.
• Biochemical and cell-based assays to evaluate compound affinity and biological activity.

Key criteria for the assessment of applicants

• Professional qualifications relevant to the PhD project
• Relevant work experience
• Publications
• The grade point average achieved
• Other professional activities
• Language skills
• The successful applicant is also required to be enterprising and to possess good interpersonal skills
  

Terms of employment

The employment as PhD fellow is full time and for 3 years.

It is conditioned upon the applicant’s successful enrolment as a PhD student at the Graduate School at the Faculty of Health and Medical Sciences, University of Copenhagen. This requires submission and acceptance of an application for the specific project to the Graduate School of Health and Medical Sciences.

The PhD study must be completed in accordance with The Ministerial Order on the PhD programme (2013) and the Faculty’s rules on achieving the degree.

The PhD student is expected to be affiliated to the graduate programme in pharmaceutical sciences, Drug Research Academy .

Salary, pension and terms of employment are in accordance with the agreement between the Ministry of Finance and The Danish Confederation of Professional Associations on Academics in the State. Depending on seniority, the monthly salary begins around DKK 27,568 (approx. 3,676 EUR) (taxable) plus pension (February 2021 level).

The first 26 months, the salary is added a mobility allowance (600 EUR per month) and (if eligible) a family allowance (500 EUR per month).

Application procedure

Your application, in English, must be submitted electronically by clicking “Apply now” below and must include the following documents in PDF format:

• Motivated letter of application (max. one page)
• CV incl. education, experience, language skills and other skills relevant for the position
• Certified copy of original Master of Science diploma and transcript of records in the original language, including an authorized English translation if issued in other language than English or Danish. If not completed, a certified/signed copy of a recent transcript of records or a written statement from the institution or supervisor is accepted.

As a prerequisite for a PhD fellowship employment, your master’s degree must be equivalent to a Danish master’s degree. We encourage you to read more in the assessment database: https://ufm.dk/en/education/recognition-and-transparency/find-assessments/assessment-database . Please note that we might ask you to obtain an assessment of your education performed by the Ministry of Higher Education and Science.

Applicants with a Master´s degree from abroad should also enclose a short description of the grading scale used

• Publication list (if possible)
• Other information to consider: References and recommendations (if possible)

The deadline for applications is 26 September 2021, 23.59pm CET

We reserve the right not to consider material received after the deadline, and not to consider applications that do not live up to the abovementioned requirements.

The further process

After the expiry of the deadline for applications, the authorised recruitment manager selects applicants for assessment on the advice of the hiring committee. All applicants are then immediately notified whether their application has been passed for assessment by an unbiased assessor.

The assessor makes a non-prioritized assessment of the academic qualifications and experience with respect to the above-mentioned area of research, techniques, skills and other requirements listed in the advertisement.

Once the assessment work has been completed each applicant has the opportunity to comment on the part of the assessment that relates to the applicant him/herself.

The applicant will be assessed according to the Ministerial Order no. 242 of 13 March 2012 on the Appointment of Academic Staff at Universities.

Interviews are expected to be held in week 42, 2021.

You can read about the recruitment process at https://employment.ku.dk/faculty/recruitment-process/

Questions

For further information, applicants may contact the principal supervisor Associate Professor Anders Bach, e-mail:  [email protected] , direct phone: +45 2128 8604 or PhD coordinator Marianne W. Jørgensen, e-mail: [email protected] , direct phone: +45 3533 6449.

For more information on working and living in Denmark visit http://ism.ku.dk (International staff mobility) and https://www.workindenmark.dk

The Faculty of Health and Medical Sciences comprises approximately 7500 students, 1500 PhD students and 3200 employees. The Faculty advances the field of health sciences through its core activities: research, teaching, knowledge sharing and communication. With basic research fields ranging from molecular studies to studies of society, the Faculty contributes to a healthy future through its graduates, research findings and inventions benefitting patients and the community. The University of Copenhagen wishes to reflect the surrounding community and invites all regardless of personal background to apply for the position. 

Part of the International Alliance of Research Universities (IARU), and among Europe’s top-ranking universities, the University of Copenhagen promotes research and teaching of the highest international standard. Rich in tradition and modern in outlook, the University gives students and staff the opportunity to cultivate their talent in an ambitious and informal environment. An effective organisation – with good working conditions and a collaborative work culture – creates the ideal framework for a successful academic career.