Postdoc in mRNA-based CAR T-cell therapy

Do you want to help improve people's health?

We are looking for a committed postdoctoral doctor with strong expertise in human immunology to develop mRNA-based car T cells and study T cell function in chronic lymphatic leukemia (KLL). We offer a stimulating and creative research environment at Karolinska Institutet where mechanistic T-cell biology meets the development of new immunotherapies against cancer.

Your role

Marcus Buggert's research group at the Center for Infectious Medicine (CIM), Department of Medicine, Huddinge, studying human T cell responses to viral infections, vaccination and cancer. Our research combines human patient materials with advanced flow cytometry, functional analyzes and single cell and multi-micro-methods. Within the KLL program we work near the clinical and technical partners to understand how disease and treatment affect T cell function and their potential for cell therapy.

You will work with a project that develops CD19 targeted car T cells using mRNA and targeted lipid nanoparticles (TLNP). The platform provides a transient car expression and developed with the goal of being able to generate car T cells directly in the body. The project examines how the distortion of disease, treatment and T cell differentiation affects the ability to eliminate malignant B cells. A central issue is the factors of both the T cells and target cells that limit the effect on the patient's own KLL cells.

The work comprises mRNA-based car T cell generation by electroporation and TLNP delivery, cultivation of primary human cells and functional co-culture attempts. With high-parametric flow cytometry and image of living cells, you will study car expression, killing kinetics and individual T cells to kill several target cells sequentially. Particular focus is on understanding and improving the cytotoxicity during the time-limited CAR expression and to evaluate repeated MRNA delivery.

The project also includes strategies for improving the function of the T cells and the availability of the car receptor on the cell surface. Functional studies are coupled to phenotypic, transcriptional and epigenetic analyzes to identify mechanisms behind reduced function and possible pathways to affect them. The goal is to create a mechanistic basis for more efficient mRNA-based car T cell therapy at KLL. You are independently expected to plan and implement experiments, analyze data and contribute to scientific publications in close cooperation with the group.

Who are you?

To be employed as postdoctoral, a doctoral degree or a foreign degree is deemed to correspond to a Swedish doctoral degree. This authorization requirement must be met at the latest at the time when the employment decision is made. It is more adventant if you have completed your doctoral degree within the last three years, if there are special reasons, your degree may have been completed before.

To qualify for the postdoctoral service, a doctoral degree is required in immunology, biomedicine, cell biology, molecular biology or a related area, as well as documented experience of experimental human immunology. You should have good experience in T cell biology, flow cytometry and functional cell-based assays. Experience of Car T cells, RNA-based cell modification or research on hematological malignancies is particularly relevant to the service.

We are looking for a person who is scientifically driven, careful and independent, but also thrives in an interdisciplinary team where experimental immunology, clinical collaborations and technology development are integrated. You should be able to drive projects forward, contribute to method development and actively participate in the group's scientific discussions. Publications that first authors are merit. Very good ability to communicate in English, both orally and in writing, is a requirement.

It is particularly merit that the applicant has

• Experience of Car T cells or other functional modification of primary human T cells
• Experience of mRNA delivery, electroporation or lipidnanoparticles
• Experience of primary patient samples, especially from B cell malignancies
• Experience of high parametric flow cytometry and cell sorting
• Experience in cytotoxicity assays, co-cultivation systems or imaging of living cells
• Knowledge of T cell differentiation, dysfunction or exhaustion at cancer
• Good knowledge of experimental design and statistical analysis

It is merit that the applicant has

• Experience of molecular biology methods, car-design, single-cell RNA-SEQ, ATAC-SEQ or bioinformatic analysis of the high-dimensional data set

What are we offering?

A creative, international inspirational environment filled with skills and curiosity. Karolinska Institutet is one of the world's leading medical universities. Here we conduct successful medical research and have the largest supply of medical education in Sweden. At KI you get to meet researchers with different research orientations that work together. It is the cross-border cooperation that contributes to KI's world-leading position in research. Several of the people you meet in healthcare are trained at KI. A close relationship with health care is important for creating training and research of the highest quality. As university, Karolinska Institutet is also a state authority. This means that you as an employee receive good benefits through our collective agreement.

Location:Flemingsberg

Read more about Marcus Buggert research grouphere and about the center of infectious medicine (CIM)here.
Ten reasons to choose Karolinska Institutet

Application

The application shall consist of the following documents, written in English or Swedish:

• Evidence of PhD
• A complete CV including the dissertation date, the title of the dissertation, former academic positions, academic title, current position, academic awards and committee work
• A complete publication list
• A summary of current work (maximum one page)

KI applies individual and differentiated wage setting according to our collective agreements Rals and Rals-T.

The application must be made via the recruitment system.

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