PhD scholarship in molecular cell biology: ubiquitin signalling in cellular metabolism - DTU Bioengineering

Do you want to be part of a team that is discovering new fundamental biological mechanisms involved in development of metabolic and immunological diseases?

An excellent opportunity is available to join Ubiquitin Signalling and Inflammation Lab at the Department of Biotechnology and Biomedicine, Technical University of Denmark (DTU), for a fully funded 3-year PhD Scholarship.

About the position and project
We are seeking an ambitious and highly motivated PhD student with a background in molecular cell biology or similar and a strong interest in understanding the molecular basis of signalling pathways in disease. The successful candidate will work under the supervision of Associate Professor Rune Busk Damgaard on a project that aims to identify novel regulatory mechanisms in metabolic signalling and how they may be involved in the development of metabolic disease and cancer. Specifically, the PhD student will investigate how ubiquitination regulates metabolic signalling and how cells respond and adapt to metabolic and inflammatory stresses.

The PhD student will use a range of methods, including molecular biology , biochemical assays , functional assays within e.g. cell death and metabolism, and advanced imaging techniques in mammalian cell culture and disease model systems to identify novel ubiquitin-dependent and disease-associated signalling mechanisms in cellular metabolism.

The main tasks in the projects will include:

• Culturing and stimulation of mammalian cells.
• Biochemical analysis of signalling pathways.
• Analysis of protein localisation to organelles or subcellular compartments.
• Analysis of protein posttranslational modifications (e.g. ubiquitination and phosphorylation) in response to metabolic stimuli.
• Analysis of protein-protein interactions and multi-protein complex formation.
• Analysis of cell fate outcomes, including inflammatory gene activation and cell death.
• Contributions to BSc/MSc student supervision and collaborative projects in the laboratory.

The PhD Scholarship is funded by the Independent Research Fund Denmark.

The Ubiquitin Signalling and Inflammation Lab uses a combination of molecular cell biology , biochemistry , and quantitative proteomics to unravel the fundamental biological processes that control crosstalk and integration between inflammatory and metabolic signalling pathways. Our ultimate aim is to identify druggable signalling mechanisms that will advance therapy for patients suffering from inflammatory diseases, metabolic disorders, and cancer.

In the past years, our lab has gained novel insights into how the Met1-linked ubiquitin-specific E3 ubiquitin ligase LUBAC and its counteracting deubiquitinase OTULIN regulate immunologic and metabolic homeostasis and how dysregulation of LUBAC and OTULIN leads to development of autoinflammation, dysmetabolism, and cancer (Damgaard et al., Cell 2016; Damgaard et al., EMBO Mol Med 2019; Damgaard et al., Cell Death Differ 2020; Jahan et al., Cell Death Differ 2021). We are now expanding these efforts to deepen our understanding of how Met1-linked ubiquitin signalling controls cellular responses to metabolic stress and how such pathways and mechanisms may contribute to disease development.

The PhD student will spearhead an ambitious project aiming to identify new molecular mechanisms by which LUBAC and OTULIN regulate the cellular response to metabolic stresses and determine cell fate. Such mechanisms may be druggable and may be involved in the development of metabolic and inflammatory diseases as well as cancer.

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/

Damgaard et al., Cell Death Differ (2020): https://pubmed.ncbi.nlm.nih.gov/30804083/

Jahan et al., Cell Death Differ (2021): https://pubmed.ncbi.nlm.nih.gov/33441937/

Qualifications and assessment criteria
The successful candidate must:

• hold a two-year master's degree (120 ECTS points), or a similar degree with an academic level equivalent to a two-year master's degree, in a relevant subject.
• have an outstanding academic record with a background in for example biomedicine. biochemistry, molecular biology, biotechnology, or immunology.
• be ambitious, curious, and highly motivated.
• have attention to details and good organisational skills.
• have the ability to work in a team as well as independently.
• have excellent communication skills in written and spoken English.
• have the persistence to work on challenging tasks and succeed in a competitive research field.

Essential skills and competences:

• Broad background knowledge in cell biology and protein biochemistry
• Practical laboratory experience in cell and/or molecular biology

The ideal candidate will have one or more of these desirable - but not essential - skills and competences:

• Research experience within any or multiple of these fields: cell signalling, metabolic signalling, inflammatory signalling, autophagy, lysosome or mitochondrial biology, or the ubiquitin system,
• Hands-on experience with mammalian cell culture and cell transfection,
• Hands-on experience with biological imaging techniques, e.g. confocal fluorescence microscopy,
• Hands-on experience with immunoblotting (Western blot),
• Hands-on experience with immuno-/affinity precipitation of protein complexes,
• Hands-on experience with molecular biology techniques, including PCR, molecular cloning, and mutagenesis,
• Experience with quantitative (image) data analysis and statistics, e.g. using R Studio, Prism, or other relevant software,
• Experience with CRISPR/Cas9-mediated gene editing.

About the research group
The successful candidate will join a vibrant,ambitious, and international research team . The Ubiquitin Signalling and Inflammation Lab offers a collaborative, supportive, and dynamic work environment focusing on excellence in research and mentoring. Read more about the lab and our research here: http://bioengineering.dtu.dk/usi

The Ubiquitin Signalling and Inflammation Lab is embedded in 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 Department offers access to a large suite of state-of-the-art core facilities, including proteomics, bioimaging, biophysics, and structural biology.

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 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.

We offer
DTU is a leading technical university globally recognized for the excellence of its research, education, innovation and scientific advice. We offer a rewarding and challenging job in an international environment. We strive for academic excellence in an environment characterized by collegial respect and academic freedom tempered by responsibility.

Salary and appointment terms
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. The period of employment is 3 years.

You can read more about career paths at DTU her http://www.dtu.dk/english/about/job-and-career/working-at-dtu/career-paths.

Starting date is 1 May 2024 (or as agreed upon by all parties). The position is a full-time position.

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 . Furthermore, you have the option of joining our monthly free seminar “PhD relocation to Denmark and startup “Zoom” seminar ” for all questions regarding the practical matters of moving to Denmark and working as a PhD at DTU.

Application procedure
Your complete online application must be submitted no later than 25 February 2024 (23:59 Danish time) .

Applications must be submitted as one PDF file containing all materials to be given consideration. To apply, please ckick "Apply now", fill out the online application form, and attach all your materials in English in one PDF file . The file must include:

• A cover letter describing your motivation, ambition, and how your technical skills are suited for the project,
• Detailed curriculum vitae (CV),
• List of publications (if any),
• Names and contact details (including email address and phone number) for two academic references.
• Master’s (M.Sc.) and Bachelor’s (B.Sc.) degree diplomas as well as grade transcripts (in English) including official description of grading scale,

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) is an international leader in the areas of biotechnology and biomedicine. Our engineering approach to all aspects of biotechnology and biomedicine positions us as a valuable player with unique competences in a growing bio-based economy and with health systems transforming towards personalized medicine. We have a clear focus on the needs in the life science- and biotech industries and point towards innovation, new businesses, and scientific services for the benefit of society. The department has extensive collaborations with national and international research units and industry. DTU Bioengineering has approx. 400 employees, of which 2/3 are scientific staff. The department is located at DTU Lyngby Campus.

Technology for people
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 mission to develop and create value using science and engineering to benefit society. That mission lives on today. DTU has 13,500 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.

Kilde: Jobnet.dk