PhD Scholarship: Ubiquitin Signalling Mechanisms in Inflammatory Disease

A 3-year PhD Scholarship starting 1 May 2022 is available in the Ubiquitin Signalling and Inflammation Laboratory led by Associate Professor Rune Busk Damgaard.

Our mission
The mission in the Ubiquitin Signalling and Inflammation Laboratory is to unravel fundamental biological concepts controlling inflammatory signalling pathways. Our aim is to identify druggable signalling mechanisms that will advance therapy for patients suffering from diseases caused by chronic inflammation and dysregulation of signalling homeostasis, including autoinflammatory conditions and cancer.

The specific interest of the lab is to understand how posttranslational modification of proteins by ubiquitin (ubiquitination) regulates cell signalling. Ubiquitin modifications control a wide variety of signalling pathways, particularly related to inflammation, immunity, and cell stress by altering protein stability, function, or protein-protein interactions. When dysregulated, ubiquitin signalling contributes to development of chronic immune disorders and cancer, however the mechanisms behind this remain unclear. The lab uses a mix of molecular cell biology, biochemistry, and -omics technologies to investigate and understand how ubiquitin modifications – particularly the enigmatic 'atypical' ubiquitin chains (M1-, K6-, K11-, K27-, K29-, K33-linked chains) – control cellular signalling in normal and disease states.  

This PhD project is part of the lab's major long-term strategy to identify ubiquitin-dependent signalling mechanisms that can be targeted pharmacologically to treat diseases related to chronic inflammatory or cell stress conditions.

The Project
The PhD student will spearhead an ambitious project aiming to identify new mechanisms in ubiquitin signalling that control cell fate decisions, transcription factor activation, and cell viability during inflammation. Such mechanisms may be druggable and could ameliorate certain aspects of autoinflammatory disease. 

The project aims to understand the mechanisms by which M1-linked (linear) ubiquitin chains control the assembly and stability of key signalling complexes that regulate cell fate decisions at the interface of inflammatory signalling and cell death. Specifically, the student will investigate how disease-associated mutations leads to impaired function of M1-linked ubiquitin signalling pathways, how this dysfunction in sensed in cells (as a stress signal), and how this stress signal leads to impaired stability of the affected signalling complex(es). The student will use molecular biology, mammalian cell culture systems, biochemical approaches, functional assays (e.g. transcription factor activation and cell survival assays), as well as quantitative mass spectrometry-based proteomics analyses performed in collaboration with the state-of-the-art DTU Proteomics Core to identify these novel, disease-associated signalling and sensing mechanisms leading to cell dysfunction.

Relevant reading:
Damgaard et al. , Cell (2016): https://pubmed.ncbi.nlm.nih.gov/27523608/
Damgaard et al. , EMBO Mol Med (2019): https://pubmed.ncbi.nlm.nih.gov/30804083/

Responsibilities and qualifications
The successful candidate holds an M.Sc. degree (or equivalent) in biochemistry, molecular biology, biomedicine, biology, immunology, or a related subject and is ambitious, curious and highly motivated.The candidate is expected to have a strong interest in fundamental scientific discoveries and their translational potential.

In addition, the candidate is expected to have:

• Hands-on experience with standard molecular biology and biochemical techniques, e.g. PCR and immunoblotting (Western blot)
• Hands-on experience with immuno-/affinity precipitation of protein complexes
• Hands-on experience with mammalian cell culture techniques
• Good background knowledge in cell biology
• Good background knowledge in molecular biology and protein biochemistry
• Experience with quantitative data analysis and statistics, e.g. using R Studio, Prism, or Excel
• The ambition, drive, and motivation to succeed within a competitive research field
• Organisational skills and the ability to work in a team as well as independently
• Excellent communication skills in written and spoken English

Experience with any of the following is highly desirable but not essential:

• Hands-on experience with mass spectrometry-based proteomics
• Experience with proteomics data analysis
• Research experience in the ubiquitin-proteasome system or related pathways
• Hands-on experience with CRISPR/Cas9-mediated gene editing

What we offer
The successful candidate will join an ambitious and international research team at the Department of Biotechnology and Biomedicine, Technical University of Denmark (DTU).The Ubiquitin Signalling and Inflammation Laboratory offers a highly ambitious, challenging, encouraging, and dynamic work environment focusing on excellence in research, teaching, and innovation. We work together as a team and grow together as scientists to tackle important, fundamental research questions. Read more about the lab and our research here: http://bioengineering.dtu.dk/usi . 

The Ubiquitin Signalling and Inflammation  Group  is part of the Department of Biotechnology and Biomedicine, Technical University of Denmark. The department is highly interdisciplinary and a leading department within life sciences in Denmark, covering both fundamental, technological, and applied aspects of biomedical research. The successful candidate will join a recently started lab with excellent funding and support. The candidate will benefit from a thriving international and collaborative community and state-of-the-art facilities with access to cutting-edge technologies and equipment.   

Approval and Enrolment
The scholarship for the PhD degree is subject to academic approval, and the candidate will be enrolled in one of the general degree programmes at DTU. For information about our enrolment requirements and the general planning of the PhD study programme, please see the DTU's rules for the PhD education .  

Assessment
The assessment of the applicants will be made by Associate Professor Rune Busk Damgaard together with relevant project partners.

Salary and terms of employment
The appointment will be based on the collective agreement with the Danish Confederation of Professional Associations. The allowance will be agreed upon with the relevant union. This is a full-time position for a fixed term of 3 years. The start date is 1 May 2022 (or as negotiated). 

The laboratory is located at Søltofts Plads, DTU Lyngby Campus (Greater Copenhagen, Denmark).

Further information
Informal enquiries and requests for further information should be directed to Associate Professor Rune Busk Damgaard ([email protected] )

If you are applying from abroad, you may find useful information on working in Denmark and at DTU at DTU – Moving to Denmark .

Application procedure
Please submit your online application no later than 6 February 2022(Danish time).  To apply, please open the link "Apply online" and fill out the online application form. The following must be attached in English:

• Cover letter describing your motivation, ambition, and technical skills
• Detailed CV
• List of publications (if any)
• Grade transcripts and BSc/MSc diploma including official description of grading scale
• Names and contact details for two academic references

You may apply prior to ob­tai­ning your master's degree but cannot begin before having received it.

Applications received after the deadline will not be considered.

All interested candidates irrespective of age, gender, race, disability, religion or ethnic background are encouraged to apply.

The Department of Biotechnology and Biomedicine (DTU Bioengineering) addresses challenges of societal and scientific importance within biotechnology, biomedicine, food technology and human health. The department is based on both basic and applied research and employs tools from biochemistry, biophysics, chemistry, cellular biology, immunology, microbial ecology and physiology, bioinformatics and bio-engineering.  The department has extensive collaboration with national and international research units and industries. DTU Bioengineering has approx. 300 employees, of which 2/3 is scientific staff. 

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DTU develops technology for people. With our international elite research and study programmes, we are helping to create a better world and to solve the global challenges formulated in the UN’s 17 Sustainable Development Goals. Hans Christian Ørsted founded DTU in 1829 with a clear vision to develop and create value using science and engineering to benefit society. That vision lives on today. DTU has 12,900 students and 6,000 employees. We work in an international atmosphere and have an inclusive, evolving, and informal working environment. DTU has campuses in all parts of Denmark and in Greenland, and we collaborate with the best universities around the world.