Postdoc position in natural killer cell biology and cell therapy

• English

PRIMA is a new Center of Excellence in Precision Immunotherapy at the University of Oslo funded by the Research Council of Norway. https://www.prima.uio.no/english/. We are now recruiting a postdoc to join a team-based alliance and contribute to the next generation immunotherapy strategies.

The current position is a 3-year postdoc position in the Malmberg Laboratory at the University of Oslo, Department for Cancer Immunology, located at the Institute for Cancer Research, Oslo University Hospital, Radiumhospitalet. https://www.ous-research.no/malmberg/. The position is available from June 1st 2024.

Immunotherapy has dramatically improved outcomes for cancer patients. A single injection of gene-modified immune cells equipped with a therapeutic receptor that targets cancer cells can cure several cancer types originating from blood cells. However, the success of gene therapy has not yet been extended to other cancer types, where two major challenges are i) difficulties in identifying safe target molecules and efficacious immune receptors that recognize them, and ii) immune-suppressive mechanisms in the tumor. The Precision Immunotherapy Alliance (PRIMA) will use the immune system of healthy donors to overcome these bottlenecks and extend cell-based immunotherapy to a range of blood and solid cancers. Novel categories of therapeutic targets that are shared among large numbers of patients can thereby be exploited. Other targets for precision immunotherapy will be identified by a combination of sophisticated computational analysis tools and experiments that identify cell types and how they interact in the tumor. A combination of gene-modified immune cells and new agents that overcome tumor defense mechanisms may radically improve cancer therapy.  Promising therapeutic modalities will be scaled-up for first-in-man clinical trials in a new infrastructure for advanced cell and gene therapy.

The Malmberg lab has a strong background in understanding the cellular and molecular mechanisms underlying the formation and diversification of human NK cell repertoires in health and disease. A central aspect of these studies has been to examine the dynamic shaping of NK cell function by killer cell immunoglobulin-like receptors (KIR). Understanding how inhibitory interactions can lead to modulation of the lysosomal compartment and how lysosomal signaling fine-tunes the functional response is one current area of research within the lab.

Another area of research includes deciphering the repertoire dynamics, as well as metabolic and functional characteristics of proliferating NK cells, both during homeostatic proliferation and targeted feeder-based expansions. Through single-cell RNA sequencing, we are looking to identify important gene regulatory circuits underlying NK cell differentiation and characterize NK cell states in healthy and malignant tissues. These studies allow us to identify novel targets to genetically optimize human NK cells in terms of metabolic tolerance, specificity and functionality for cell-based immunotherapies.

Through industry collaboration, the lab is genetically optimizing synthetic killer cells (iPSC-derived NK) to develop an off-the-shelf precision immunotherapy product. The overall aim of the Malmberg lab is to design and implement, through clinical trials, novel strategies for NK-cell based immunotherapy to treat patients with advanced cancer.

The Malmberg lab is located in Oslo/Norway and Stockholm/Sweden and currently consists of 20 people. The post-doc position is based at the Oslo node of the group, at the Department of Cancer Immunology, Institute for Cancer Research. https://www.ous-research.no/institute/. The physical location within Oslo University Hospital and access to GMP facilities (ACT) facilitates translational research within the lab, with one clinical trial already completed and another one starting up.

Advances in genetic engineering combined with the rise of single cell methods and advanced subcellular imaging technologies, have opened up new and exciting opportunities to study immunology. We are seeking a highly motivated and self-driven postdoc who has a keen interest in basic immunology and translational research.

Broadly speaking, the research project aims at improving cell-based immunotherapy through a deeper understanding of the functional regulation of NK cells. The project will decipher subcellular processes in NK cells, including inter-organelle communication through ion channels, positioning and trafficking of molecules within the cell, energy usage, and how these regulate effector functions in NK cells at different time-scales. Experiments using various types of perturbations, including mechanical forces, metabolic stress and hypoxia will be implemented to identify pathways that make NK cells more resilient to the suppressive tumor microenvironment. Insights from these fundamental biological studies pave way for synthetic engineering of the functional NK cell template for off-the-shelf cell therapy.

Laboratory work will include a variety of single cell technologies, such as confocal microscopy and live cell imaging, high-dimensional immune profiling by flow cytometry, single-cell indexed FACS-sorting and RNA sequencing. Additionally, viral transduction and CRISRP/Cas9 will be used to genetically engineer primary NK cells, NK cell lines and/or iPSC-derived NK cells. 3D killing assays will be implemented to monitor and evaluate the function of the engineered NK cells, such as cytotoxicity, migration and proliferation, in a complex environment.Description project

The postdoc is expected to design and conduct experimental studies, perform data and statistical analysis, collaborate on related projects both within the lab (KI/Oslo) and outside the lab (collaborators) and attend, present and discuss at lab meetings and journal clubs.

We are looking for a highly motivated and structured candidate with excellent laboratory skills, analytic and collaborative qualities.

• The candidate must have a project relevant PhD
• Documented subject knowledge of relevance to the area of research including imaging, immunological research, multiparameter flow cytometry and primary cell culture.
• Experience in synthetic biology, vector design and cell engineering is an advantage
• The candidate must be fluent in written and spoken English.

The appointment requires a PhD or a degree equivalent to a Norwegian PhD in natural or medical sciences. A prerequisite for applicants who have not yet defended their thesis is that the thesis is submitted for assessment before the closing date for applications. Appointment to the position is dependent on the public defense of the doctoral thesis being approved.

• A professionally stimulating and friendly working environment
• Salary NOK 575 400 - NOK 657 300 per annum depending on qualifications in position as Postdoctoral Research Fellow (position code 1352)
• Attractive welfare benefits and a generous pension agreement, in addition to Oslo’s family-friendly environment with its rich opportunities for culture and outdoor activities
• A career development program for postdoctoral fellows The Postdoctoral Programme - Faculty of Medicine (https://www.med.uio.no/english/research/postdoctoral-programme/) 
• Interest organization for PhD and postdoctoral fellows Home – UiODoc (https://foreninger.uio.no/uiodoc/)

The application must include:

• Application letter, including a ½ page motivation statement and research interests
• CV (summarizing education, positions, academic work-scientific publications and other relevant activity)
• Copies of educational certificates and letters of recommendation
• List of publications and academic work that the applicant wishes to be considered by the evaluation committee. Note: Applicants are advised not to attach the original publications, only provide a list.
• Names and contact details of 2-3 referees (name, relation to candidate, e-mail and telephone number).

The application with the required attachments should preferably constitute as few files as possible, preferably 1-2 files.

The application with attachments must be delivered in our electronic recruiting system. Foreign applicants are advised to attach an explanation of their University's grading system. Please note that all documents should be in English (or a Scandinavian language).

In assessing the applications, special emphasis will be placed on the documented, academic qualifications, the project description (whenever this is required in the call for applicants), and the quality of the project as well as the candidates motivation and personal suitability. Interviews with the best qualified candidates will be arranged.
It is expected that the successful candidate will be able to complete the project in the course of the period of employment.

Information about the project can be addressed to Professor Karl-Johan Malmberg, [email protected]

Information about the electronic application form can be addressed to Human Resources Adviser Andreas Hessen Solheim, [email protected].

Please see the guidelines and regulations for appointments to Postdoctoral fellowships at the University of Oslo.

No one can be appointed for more than one Postdoctoral Fellow period at the University of Oslo.

According to the Norwegian Freedom of Information Act (Offentleglova) information about the applicant may be included in the public applicant list, also in cases where the applicant has requested non-disclosure.

Inclusion and diversity are a strength. The University of Oslo has a personnel policy objective of achieving a balanced gender composition. Furthermore, we want employees with diverse professional expertise, life experience and perspectives.

If there are qualified applicants with disabilities, employment gaps or immigrant background, we will invite at least one applicant from each of these categories to an interview.

The University of Oslo is Norway’s oldest and highest ranked educational and research institution, with 28 000 students and 7000 employees. With its broad range of academic disciplines and internationally recognised research communities, UiO is an important contributor to society.

The Institute of Clinical Medicine (Klinmed) is one of three institutes under the Faculty. Klinmed is responsible for the Faculty's educational and research activities at Oslo University Hospital and Akershus University Hospital. With about 800 employees spread over approximately 425 man-labour years, Klinmed is the university's largest institute. Our activities follow the clinical activity at the hospitals and are spread across a number of geographical areas.

8th May 2024

University of Oslo

Oslo

Scope

Fulltime (1 positions) Fulltime (%)

Fixed Term

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