Doctoral (PhD) student position in cancer cell plasticity

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 subject area of Laboratory Medicine brings together basic scientific research, clinical research, and healthcare. As a result, the Department holds a strategic position with good conditions for translational research, thanks to its strong basic scientific capability and span, high technical content and access to clinical problems and clinical materials. The role of the Department is to transfer medical knowledge and improve it within healthcare, in collaboration with academia, healthcare services and industry actors. LabMed is the third largest teaching department at KI, and is involved in 10 of the 19 first-cycle programmes at the Institute.

Ninety percent of all cancer deaths arise from tumor metastasis. Our research focuses on the process when tumor cells migrate from the tumor to blood and lymph vessels where they can spread to other parts of the body. Our goal is a better understanding of the complex mechanisms behind metastasis and that our results in the long-term can be applied in the clinic. The process of metastasis depends on the delamination and spread of tumor cells. Only a minority of the tumor cells, i.e. tumor-initiating cells also referred to as cancer stem cells (CSCs), are capable of successfully seeding a distant site. The CSC hypothesis proposes that only a subset of tumor cells have the ability to self-renew and are thus responsible for driving tumorigenesis, making them ideal targets for cancer intervention.

Our research group focuses on the early steps of the metastatic process, i.e. migration and invasion of the tumor cells into circulation through cell plasticity programs and the mechanisms controlling these processes. Our long-term goal is that these studies will provide significant insight into the complex mechanism of tumor spread and metastasis and ultimately allow our research to advance into a clinical setting.

Currently, we have several ongoing national and international research projects within these areas and our laboratory places a special focus on international collaborative efforts. It is our ambition to create a unique laboratory and educational environment that is not limited by departmental or national barriers but only by our scientific education, curiosity and ambition.

Glioblastoma multiforme (GBM), is the most clinically aggressive form of glioma. Despite progress in adopting a multidisciplinary treatment approach the median survival time for patients with GBM is only 14.6 months. GBM migration and infiltration into the extra-tumoral brain tissue reduces complete surgical resection success. GBM cells stop proliferating prior to activating cell migration programs, making these cells resistant to chemo- and radio-therapies, which are most effective against rapidly dividing cells. There are three major GBM transcriptional subtypes identified by bulk RNA-seq: pro-neural (PN), classical (CL), and mesenchymal (MES). However, these subtypes display high intra-tumoral plasticity in single cell RNA-seq, with the different transcriptional subtypes coexisting within cell populations in any given tumor. This plasticity allows GBM cells to transition among cell states as required by their microenvironment challenges, such as hypoxia, nutrient depletion and cytokine stimulation. A prime example of this concept and major mechanism of GBM pathogenesis is the cellular transition from the proliferative PN to the migratory MES state, a cell identity switch known as the PN to MES Transition (PMT). The MES subtype is the most aggressive and migratory form of GBM. This tumor cell plasticity program was recently suggested to share key features of the well-known Epithelial to Mesenchymal (EMT) program, which induces cell cycle arrest, migration, stem cell phenotypes, immune evasion and resistance to chemotherapies that target highly proliferative cells. However, the PMT program in GBM has yet to be fully characterized, especially with regard to the nature of stimuli responsible for its activation and execution. A deeper understanding of the initiation, regulation, and execution of PMT would expand the repertoire of potential therapies specifically targeting the temporary cell cycle-halted, brain-infiltrating GBM cells that fuel invasion into healthy brain and disease progression.

The PhD project will investigate different inducers of PMT and explore the mechanism by which PMT is induced and how PMT can be therapeutically targeted. The student will be required to work with in vitro and in vivo glioma samples and perform laboratory techniques including mRNA analysis (qPCR), protein expression analysis (Western blot), immunocytochemistry, immunohistrochemistry, chromatin immunoprecipitation, animal studies etc.

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 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:

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 .

We seek a student with a background in molecular biology, biomedicine or the equivalent. The candidate should have a good team spirit, be self-motivated and a keen interest in cancer cell biology.

Experience in working with glioma samples, molecular biology techniques, chromatin immunoprecipitation, m6A methylation assays are a strong merit. An experience in radiation studies is also an advantage. The student is required to have good communication skills in English (written and verbal).

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

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)

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.