PhD student position in Chromatin Biology

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 Baranello lab: Drawing from our expertise in the fields of topoisomerase and cancer biology, we aim to answer fundamental questions about how transcription, replication and DNA topology are functionally coordinated in human cells. We use state-of-the-art approaches to assess transcriptomic, epigenomic and replisomic profiles, as well as bioinformatics, microscopy and drug screens to understand how topoisomerase regulation affects fundamental nuclear processes (key lab references: Baranello et al. Cell 2016; Wiegard et al. Molecular Cell 2021; Das et al. Molecular Cell 2022). The overall aim is to reveal novel cancer dependencies and develop new anti-cancer strategies more specific towards tumor cells and with fewer side-effects.

We are a young and dynamic research team with a well-established collaborative network. The group is also associated to the laboratory of Dr. Levens at the National Institutes of Health in the US. The successful applicant will thus be part of multiple networks of recognized scientists. The group is placed in the Biomedicum, a top modern research building with a large repertoire of researchers and access to state-of-the-art infrastructure and facilities.

Topoisomerases are essential enzymes that regulate the topology of DNA favoring replication and transcription by cleaving/resealing DNA strands. Because cancer cells have higher rates of proliferation compared to normal cells, they are highly dependent on topoisomerase activity. Therefore, strategies to target topoisomerases could provide a mean to selectively affect cancer cells.

The focus of this research project is to understand how topoisomerases are regulated during nuclear processes to develop new ways to target these regulatory mechanisms and affect the viability of cancer cells. Recent evidence show that topoisomerases execute their function through interactions with partner proteins that modulate their activity to affect transcription (Baranello et al. Cell 2016; Das et al. Molecular Cell 2022). We will use biochemical and molecular biology approaches, microscopy, single molecule tracking, DNA and RNA sequencing and CRISPR-based genome editing to investigate how topoisomerase dynamics within the nucleus controls topoisomerase activity. The outcome of the PhD work will inspire a new strategy to target topoisomerases in cancer therapy.

The PhD program at the Karolinska Institutet corresponds to 4 years full time studies. The project is a combination of practical laboratory work (wet-lab work) and computational analysis (programming in R and/or Python). The program also includes attendance at seminars, courses, and conferences. The PhD student will plan and execute experiments, analyze data, interpret, and present the results as well as write scientific articles, initially under supervision but with greater independence going forward.

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 curious, highly motivated and creative student with a background in transcription dynamics, condensate regulation and DNA topology, with an interest in learning programming languages to analyze sequencing and microscopy data. The candidate should have a good team spirit and bring a keen interest in solving intricate scientific questions in chromatin biology. Experience with mammalian cell cultures, protein biochemistry, live-cell and confocal imaging, next-generation sequencing and large-scale bioinformatics analysis is a strength. Excellent interpersonal and communication skills (in English written and verbal) is required. Emphasis will be also placed on personal suitability, fitting well into the current research group.

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.