Doctoral student in virus-host interactions and immunometabolism

Doctoral Student In Virus-Host Interactions And Immunometabolism

To be a doctoral student means to devote oneself to a research project under supervision of experienced researchers and following an individual study plan. For a doctoral degree, the equivalent of four years of full-time doctoral education is required.

The doctoral student will join the Systems Virology Lab, Division of Clinical Microbiology, Department of Laboratory Medicine at Karolinska Institutet, and will participate in the MERIT Marie Skłodowska-Curie Actions (MSCA) Doctoral Network.

Our research focuses on virus-host interactions and the molecular mechanisms regulating antiviral immunity, immune evasion, immunometabolism and cellular homeostasis. We combine molecular and cellular virology with advanced experimental models and systems-level approaches to investigate how viruses reprogramme host cells and how these processes influence viral pathogenesis and disease. The doctoral student will work in a multidisciplinary and international research environment and interact closely with researchers within the Center for Systems Infection Biology and the wider MERIT network.

The project, “Mechanisms of PLpro-mediated host-cell reprogramming in SARS-CoV-2 infection and persistence” (DC14), will investigate how the SARS-CoV-2 papain-like protease (PLpro) alters host-cell functions through its deISGylating, deubiquinating and broader immune-modulatory activities.

ISG15 is an interferon-stimulated ubiquitin-like modifier involved in antiviral immunity and the regulation of cellular processes, including metabolism and mitochondrial function. The project will investigate how PLpro-mediated modulation of ISG15-and ubiquitin-dependent pathways affects antiviral signalling and host-cell metabolism, and how these changes influence SARS-CoV-2 infection and persistence in physiologically relevant experimental models.

The doctoral student will:

• Define how PLpro-mediated modulation of host ubiquitin and ubiquitin-like pathways, with particular focus on deISGylation, reprogrammes host-cell metabolism and antiviral signalling during SARS-CoV-2 infection, integrating molecular, biochemical and cellular approaches.
• Determine how PLpro-driven host-cell reprogramming shapes SARS-CoV-2 persistence in physiologically relevant models, including gut and lung organoid systems.
• Explore broader consequences of PLpro-mediated persistence, including links to chronic inflammation and neuroinflammation, using advanced organoid systems and patient-derived tissue where appropriate.

  The doctoral student will be directly supervised by Dr. Soham Gupta (main supervisor) and Dr. Magdalini Lourda. The project will be carried out in close synergy with the broader team at the Center for Systems Infection Biology, including network PIs Dr. Ujjwal Neogi and Dr. Iva Filipovic, providing access to complementary expertise in single-cell techniques, spatial multi-omics and immunometabolic engineering.

  A central component of the MSCA Doctoral Network is international and interdisciplinary training. Planned secondments include Complex tissue and barrier models with Dr. Adithya Sridhar, Amsterdam UMC, the Netherlands and Metabolic alteration analysis with Prof. Gisa Gerold, Medical University of Innsbruck, Austria. The doctoral student will also participate in MERIT-wide scientific meetings, hands-on workshops, and transferable-skills training.

  A creative and inspiring environment full of expertise and curiosity. Karolinska Institutet is one of the world's leading medical universities. Our vision is to pursue the development of knowledge about life and to promote a better health for all. At Karolinska Institutet, we conduct successful medical research and hold the largest range of medical education in Sweden. As a doctoral student you are offered an individual research project, a well-educated supervisor, a vast range of elective courses and the opportunity to work in a leading research group. Karolinska Institutet collaborates with prominent universities from all around the world, which ensures opportunities for international exchanges. You will be employed on a doctoral studentship which means that you receive a contractual salary. Employees also have access to our modern gym for free and receive reimbursements for medical care.

  In addition, the position offers participation in an international MSCA Doctoral Network, including research secondments, network-wide scientific training, transferable-skills courses and collaboration with academic and non-academic partners across Europe.

  It is your responsibility to certify eligibility by following the instructions on the web page Entry requirements (eligibility) for doctoral education.

  You meet the general eligibility requirement for doctoral/third-cycle/PhD education if you:

  1. have been awarded a second-cycle/advanced/master qualification (i.e. master degree), or
  2. have satisfied the requirements for courses comprising at least 240 credits of which at least 60 credits were awarded in the advanced/second-cycle/master level, or
  3. have acquired substantially equivalent knowledge in some other way in Sweden or abroad.

     Follow the instructions on the web page Entry requirements (eligibility) for doctoral education.

     You meet the specific eligibility requirement for doctoral/third-cycle/PhD education if you:

     – Show proficiency in English equivalent to the course English B/English 6 at Swedish upper secondary school.

     Follow the instructions on the web page English language requirements for doctoral education.

     Verification of your documents Karolinska Institutet checks the authenticity of your documents. Karolinska Institutet reserves the right to revoke admission if supporting documents are discovered to be fraudulent. Submission of false documents is a violation of Swedish law and is considered grounds for legal action.

     Additional MSCA Doctoral Network eligibility requirements: In addition to Karolinska Institutet's eligibility requirements for doctoral education, applicants must fulfil the eligibility conditions of the MSCA Doctoral Network. At the time of employment, applicants must not hold a doctoral degree and must comply with the MSCA mobility rule: they must not have resided or carried out their main activity (work, studies, etc.) in Sweden for more than 12 months in the 36 months immediately preceding the employment date.

     We are looking for a highly motivated candidate with a strong interest in virus-host interactions, molecular virology, immunology and cell biology. The applicant should have:

     • Relevant theoretical and/or experimental knowledge in molecular biology, cell biology, virology, immunology, biochemistry or a related field.
     • Experience with laboratory-based biomedical research.
     • Good analytical and problem-solving abilities.
     • The ability to work both independently and collaboratively in a multidisciplinary and international research environment.
     • Good written and oral scientific communication skills.

       Experience in one or more of the following areas will be considered particularly advantageous:

       • Protein biochemistry: protein handling, Western blotting, functional enzyme assays/kinetics or analysis of protein-protein interactions.
       • Cell and molecular biology: mammalian cell culture, molecular cloning, reporter assays or analysis of cellular signalling pathways.
       • Advanced cell models: primary cells, 3D cultures, organoids or iPSC-derived models.
       • Virology and molecular immunology: virus-host interactions, antiviral immunity, innate immune signalling or cell-type-specific host responses.
       • Histology and imaging: tissue processing, immunohistochemistry, multiplex immunofluorescence, in situ approaches or confocal microscopy.
       • Quantitative/data analysis: analysis of imaging, transcriptomic, proteomic or other biological datasets.

         Personal suitability, motivation to undertake doctoral education, scientific curiosity and the ability to collaborate effectively will be important in the overall assessment.

         The doctoral student will be employed on a doctoral studentship maximum 4 years full-time.