PhD fellowship: biochemical and molecular function of ubiquitin-directed protease DDI2, in the Svejstrup laboratory, Department of Cellular and Molecular Medicine (ICMM)

We are offering a PhD fellowship for a talented and highly motivated student interested in investigating thebiochemical and molecular function of ubiquitin-directed protease DDI2. The successful candidate will be employed in the Svejstrup laboratory at the Institute of Cellular and Molecular Medicine (ICMM) at the Faculty of Health and Medical Sciences, University of Copenhagen.

ABOUT THE LAB AND THE INSTITUTE
In September 2020, the Svejstrup Laboratory re-located from the Francis Crick institute in London to the ICMM (https://icmm.ku.dk/english/research-groups/svejstrup-group/research-group/ ).

The Svejstrup’s laboratory focuses on various aspects of gene expression, transcription-associated genome instability, the cellular response to DNA damage and the maintenance of cellular proteostasis. Details of recent papers and current research projects can be found in the link above.

Research techniques used in the laboratory include molecular cell biology, biochemistry (including protein purification, proteomics, and reconstitution of key processes with purified factors in vitro) and modern genome-wide techniques (ChIP-Seq, RNA-Seq, TT-Seq, etc), as well as genomic screening (siRNA and CRISPR screens).

Svejstrup lab represents cutting-edge interdisciplinary research and training and is located at the Panum Institute (18.6) within the ICMM. We have access to state-of-the-art facilities for mass spectrometry, flow cytometry, cell engineering, and next-generation sequencing.

Project description
The project will be an investigation of the biochemical and cellular function of the DDI2 protease, required for maintaining proteostasis during cellular stress (Dirac-Svejstrup et al., Molecular Cell 2020). DDI2 protease targets the transcription factor NRF1. NRF1 is normally associated with the ER. However, during proteasomal stress, proteolysis by DDI2 releases NRF1, and this cleaved form enters the nucleus and up-regulates proteasome genes. In this way, proteasome inhibition feeds back to transcription and results in up-regulation of the proteasome, via DDI2 protease activity. Proteasome inhibitors are now widely used in cancer therapy, so this has obvious clinical implications. Indeed, if upregulation of proteasome expression could be prevented through combination therapy with DDI2 inhibitors, the potency of the proteasome inhibitors that have transformed the treatment of blood cancers should be dramatically increased.

Our recent data provided a breakthrough by showing that purified DDI2 protease directly cleaves NRF1 in a site-specific fashion, but only when NRF1 is highly poly-ubiquitylated. So, DDI2 is the first ubiquitin-directed, site-specific protease to be discovered (Dirac-Svejstrup et al., Molecular Cell 2020). The project will involve one or more of the following: 1) defining the functional domains of DDI2, and their role in its biology; 2) inhibition of DDI2 with small-molecule inhibitors and 3) discovering other DDI2 targets, and charaterizing how they are processed by DDI2 protease.

Principal supervisor isProfessor Jesper Svejstrup, ICMM, e-mail: [email protected] .

Start:            December 2022 or soon thereafter.
Duration:      3 years as a PhD fellow. 

Job description
Your key tasks as a PhD student at SUND are:

• Carry through an independent research project under supervision.
• Complete PhD courses or other equivalent education corresponding to approx. 30 ECTS points.
• Participate in an active and ambitious research environments including a stay at another research team.
• Obtain experience with teaching or other types of dissemination related to your PhD project.
• Teach and disseminate your knowledge.
• Write a PhD thesis on the grounds of your project.

Key criteria for the assessment of applicants
Applicants must have qualifications corresponding to a master’s degree Biochemistry, Biology, Biomedicine or similar (equivalent of the Danish candidate, 3 + 2 years) related to the subject area of the project.

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.

Other important criteria are:

• The grade point average achieved.
• Professional qualifications relevant to the PhD project.
• Previous publications.
• Relevant laboratory experience in molecular cell biology or biochemistry.
• Other professional activities.
• Curious mind-set with a strong interest in gene expression, transcription-associated genome instability, and the maintenance of cellular proteostasis.
• Excellent English skills, written and spoken.

Place of employment
The place of employment is at the Department of Cellular and Molecular Medicine (ICMM), University of Copenhagen. Our lab at the ICMM offers a creative and ambitious scientific environment, with nine different nationalities presently represented and English as the working language. We strive to produce research results with high international impact, focusing on the functional cell, its genetic components, and molecular cellular mechanisms in a medical context.

The ICMM currently comprises five research programs, three high profile Research Centers as well as a number of internationally renowned research groups.

The scientists at ICMM are involved in high quality research based undergraduate and graduate teaching programs at the University of Copenhagen.

More information can be found at https://icmm.ku.dk/english/ .

Terms of employment
The employment as PhD fellow is full time (37 working hours per week in average) and for three 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 formulated by the applicant.

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. Salary, pension, and terms of employment are in accordance with the agree­ment between the Ministry of Taxation and The Danish Confederation of Professional Associations on Academics in the State. Depending on seniority, the monthly salary starts at approx. DKK 28,448 / EUR 3,793 (October 2022-level) plus pension.

Questions
For specific information about the PhD fellowship, please contact the principal supervisor.

General information about PhD study at the Faculty of Health and Medical Sciences is available at the Graduate School’s website: https://healthsciences.ku.dk/phd/guidelines/ .

Application procedure
Your application must be submitted electronically by clicking ‘Apply now’ below. The application must include the following documents in PDF format: 

Application deadline: Sunday 18 September 2022, 23.59 p.m. 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 above mentioned requirements.

The further process
After the expiry of the deadline for applications, the authorized recruitment manager selects applicants for formal 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. 

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

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

The Faculty of Health and Medical Sciences comprises approximately 8,000 students, 1,790 PhD students and 5,100 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.