项目介绍

2025年2月25日

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.

We are looking for an ambitious doctoral candidate that will work on advancing our understanding of how DNA topology and topoisomerase activity is linked to oncogenic translocations, with the aim of developing strategies to prevent such mechanism in cancer patients.

The research group

TheBaranello 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 single molecule assays 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; Cameron et al. Science Advances 2023). The overall aim of our research is to reveal novel cancer dependencies and develop strategies specific towards tumor cells.

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 USA, Prof. Shirahige at Tokyo University, Japan, and Prof. Nishiyama at Nagoya University, Japan. The successful applicant will thus be part of multiple networks of recognized scientists. The group is located in the Biomedicum, a top modern research building with a large repertoire of researchers and access to state-of-the-art infrastructure and facilities.

The doctoral student project and the duties of the doctoral student

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 the activity of the topoisomerase is regulated at repetitive elements in connection with genome folding and chromosomal translocations. The overarching goal is to develop strategies to modulate these regulatory mechanisms and prevent genomic translocation in cancer patients. We will use biochemical and molecular biology approaches, DNA and RNA sequencing and CRISPR-based genome editing to investigate the relationship between genome dynamics and topoisomerase activity.

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 to 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.

Skills and personal qualities

We are looking for a highly motivated, driven, enthusiastic person interested in our area of research, and ready to explore new avenues in science. The candidate should have a strong collaborative approach to research, be a team player as capable of working independently and contribute to a good social environment in the laboratory.

Requirements:

• Strong expertise in cell and molecular biology
• Expertise in genomics
• Expertise in transcription regulation
• Expertise in DNA topology
• Proficiency in scientific programming (e.g., R/Bioconductor, Python, UNIX)
• Interest in solving intricate scientific questions and willingness to help master students.
• Excellent interpersonal and communication skills (in English written and verbal). Emphasis will be also placed on personal suitability, fitting well into the current research group.

What do we offer?

The Baranello lab is eager to provide the student with an opportunity to develop and/or apply state-of-the-art methodologies to solve timely biological key questions. Necessary training on sequencing technologies and computational analysis will be given to the student. We are eager to give the candidates opportunity to become an independent researchers in interdisciplinary science within 4 years.

Visit Baranello Lab: https://ki.se/en/research/groups/topoisomerases-chromatin-biology-and-cancer-laura-baranellos-group

Visit Department of Cell and Molecular Biology: https://ki.se/en/cmb/department-of-cell-and-molecular-biology

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 requirementYou 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

[Enter here skills and personal qualities necessary or desirable/advantageous for this project and for the ability to reach the outcomes of the doctoral education. Make it clear for the applicants what is necessary and what is only desirable. It is important that this section is well thought-through in order to help in the selection process.]

Terms and conditions

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