Doctoral (PhD) student position in natural killer cell biology - Hiring in process/Finished, not possible to apply

Do you want to contribute to top quality medical research?

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 research group

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 Stockholm/Sweden and Oslo/Norway and currently consists of 14 people. The PhD position is based at the Stockholm node of the group, at the Center for Infectious Medicine (CIM), Department of Medicine, Huddinge, Karolinska Institutet. At the Center for Infectious Medicine research focuses on studies of the human immune system and CIM’s vision is to be a world leading translational research center within immunology. The proximity to Karolinska University Hospital and access to GMP facilities (Vecura) facilitates translational research within the lab, with one clinical trial already completed and another one starting up. Through the Oslo node, the Malmberg lab is part of a new Center of Excellence, the Precision Immunotherapy Alliance (PRIMA). PRIMAs aim is to overcome immune tolerance to advanced cancers through the development of gene-modified cell therapies by exploiting donor-derived immunity and modulating the tumor microenvironment.

The doctoral student project and the duties of the doctoral student

Advances in genetic engineering combined with the rise of single cell methods and the plethora of computational tools to handle large datasets have opened up new and exciting opportunities to study immunology. We are therefore seeking a highly motivated and self-driven PhD student who has a keen interest in basic immunology and translational research.

Broadly speaking, the research projects consist of genetically engineering human NK cells to improve NK cell immunotherapy and dissect NK cell biology. Focus will be placed on understanding NK cell functionality by dissecting the genetic regulatory circuits that shape the interior of the cell. Single-cell RNA sequencing datasets and previous studies in the group have identified genes of interest related to vesicular transport. This PhD project will aim to understand how the interior signaling of an NK cell dictates the functional properties of the cell, in terms of cytotoxicity, proliferation and cellular migration.    

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. Through collaboration with Björn Önfelt’s group at SciLife, we will be able to perform live cell imaging in microwells to further characterized the behavior of the edited NK cells.

Doctoral studies at Karolinska Institutet correspond to 4 years of full-time studies, which includes courses, seminars, laboratory work and presenting scientific results at meetings and conferences. The doctoral student 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.

What do we offer?

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.

Eligibility requirements for doctoral education

In order to participate in the selection for a doctoral position, you must meet the following general (A) and specific (B) eligibility requirements at latest by the application deadline.

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

A) General eligibility requirement

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.

*If you claim equivalent knowledge, follow the instructions on the web page Assessing equivalent knowledge for general eligibility for doctoral education.

B) Specific eligibility requirement

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.

(A) and (B) can only be certified by the documentation requirement for doctoral education.

Skills and personal qualities

The successful candidate must:

Be highly motivated, self-driven and have a keen interest in basic molecular immunology

Have completed a higher degree of education within medicine, molecular biology, biomedicine, genomics or biochemistry

Have previous experience with immunological research and primary cell culture

A documented ability to independently carry out experiments/small research projects (eg reference letter)

Be proficient in writing and speaking English

Desirable:

Previous experience in gene-editing, imaging and flow cytometry is highly advantageous

Understanding of bioinformatic analysis of single-cell data (R or Python) is of great merit

Terms and conditions

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

Application process

Submit your application and supporting documents through the Varbi recruitment system. Use the button in the top right corner and follow the instructions. We prefer that your application is written in English, but you can also apply in Swedish.

Your application must contain the following documents:

- A personal letter and a curriculum vitae
- Degree projects and previous publications, if any
- Any other documentation showing the desirable skills and personal qualities described above
- Documents certifying your general eligibility (see A above)
- Documents certifying your specific eligibility (see B above)

Selection

A selection will be made among eligible applicants on the basis of the ability to benefit from doctoral education. The qualifications of the applicants will be evaluated on an overall basis.

Karolinska Institutet uses the following bases of assessment:

- Documented subject knowledge of relevance to the area of research
- Analytical skill
- Other documented knowledge or experience that may be relevant to doctoral studies in the subject.

All applicants will be informed when the recruitment is completed.

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