Doctoral (PhD) student position in Liver Metastases Biology
The Department of Biosciences and Nutrition performs research and education in several areas of medical science including aging, molecular endocrinology, cancer biology, functional genomics, systems biology, epigenetics, structural biochemistry, bioorganic chemistry, cellular virology, and nutrition. It offers an excellent international research and working environment, including around 250 scientists, students, administrative and technical personnel. The Department resides in the new biomedical research building Neo, aimed at being a creative and open environment that enables meetings, synergies, and exploration of areas of mutual interest across disciplines.
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 research group of Marco Gerling https://ki.se/en/bionut/signalling-and-cellular-heterogeneity-in-cancer-marco-gerling-leander-blaas-rune-toftgard studies metastatic invasion of cancer cells into the liver. Their focus lies on liver metastases of colorectal and pancreatic cancer, which are the main cause of death for patients with these cancer types. The group investigates the molecular and cellular mechanics of liver metastases invasion. They use mouse models, explant cultures and confocal 2-photon live cell imaging to track invading metastatic cells. In order to chart cell types and cell-cell interactions, they apply single-cell sequencing of mouse and human tissue based on novel sc-sec methodologies e.g., https://www.biorxiv.org/content/10.1101/2020.03.06.980243v1
The preclinical research is tightly connected to Karolinska University Hospital, a national center for liver and pancreatic surgery. A particularly close collaboration is established with the pathology department, allowing access to retrospective cohorts of patients with liver metastases. The group leader is working halftime as physician in oncology, and all projects are strongly translational. Key collaborations relevant for the project are established with the groups of Peter Vermeulen, Antwerp Belgium (liver metastases pathology), and Martin Enge (single cell-based translational oncology), Karolinska campus Solna.
The doctoral student project and the duties of the doctoral student
One main goal of the PhD project is to establish, improve and use versatile ex vivo models of metastatic invasion in the liver.
The main questions to be tackled with these models are:
- How do malignant cells invade into the alien host organ and replace its parenchyma?
- Which essential pathways and cell-cell interactions promoting metastasis are targetable?
The overarching aim is to manipulate the key signaling pathways and cellular interactions that orchestrate metastatic invasion, in order to dissect their functions. Although the project has a focus on mouse experiments and ex vivo cultures, all experiments are tightly connected to patient material, which is used for both hypotheses generation and validation of results.
In the doctoral project, the student will functionally validate hypotheses generated by combining histopathological assessments and sc-RNA seq results. For ex vivo imaging, the student will use 2-photon confocal imaging to quantify metastases invasion. To manipulate metastatic cells and their microenvironment, the student will use CRISPR/cas9-based genome editing. For this, mice with constitutive and cell-type specific expression of Cas9 will be used, partly in vivo, partly to generate explant cultures. Genetic manipulation will be complemented by pharmacological inhibition of candidate pathways. To map in detail the effects of manipulating given pathways, sc-RNA seq of explants will be used.
Finally, the student will participate in sc-RNA seq of human tumors, and work with the pathologists to confirm the results in clinical material.
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:
- have been awarded a second-cycle/advanced/master qualification (i.e. master degree) or
- 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
- 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.
Skills and personal qualities
The ideal candidate is curiosity-driven and particularly interested in performing translational research that combines different wet lab techniques, bioinformatics and clinical pathology. The project requires integrating results from these disciplines and as such demands broad knowledge and genuine interest in the fundamental research question. Interacting with researchers and medical doctors of the different specialties requires good skills in personal communication and an openness for diverse perspectives.
Experience with organoid culture or with liver cell culture is an advantage. Knowledge of general principles of data analysis in R is advantageous, but not required, as is previous experience with confocal microscopy.
Documented knowledge of histopathology is a particular plus.
Terms and conditions
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.
Your application should contain the following documents. We prefer that your application is written in English, but you can also apply in Swedish:
- 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.
Want to make a difference? Join us and contribute to better health for all
Type of employment PhD placement
Contract type Full time
Reference number STÖD 2-4822/2020
Marco Gerling, PI , +46-76-416 74 35
Thomas Tinglöv, Head of Administration, +46-8-524 835 49
Henry Wölling, SEKO, +46-8-524 840 80
Anders Lindholm, OFR, +46-8-524 810 12
Chandrashekar Bangalore Revanna , SACO, +46-73-083 98 85
Last application date 14.Mar.2021 11:59 PM CET
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