Karolinska Institutet, Department of Medical Biochemistry and Biophysics, Translational Medicine and Chemical Biology

A doctoral student is admitted to third-cycle/doctoral education. A doctoral education consists of supervised research, combined with courses and other educational activities. An individual study plan is established for each doctoral student. For a doctoral degree, the equivalent of four years of full-time doctoral education is required.

A doctoral position funded through the Marie Sklodowska-Curie Integrative Training Network ‘aDDRess’ is available in the Crosetto group in the Bienko-Crosetto Laboratory for Quantitative Biology of the Nucleus (https://bienkocrosettolabs.org).
The main research project associated with this position consists in building an atlas of genome fragility in normal and cancer cells, and studying the relationship between genome fragility and DNA copy number alterations in cancer cells.
The primary task of the doctoral student will be developing and applying advanced bioinformatic tools to analyze large datasets obtained through various next-generation sequencing based methods, including the BLISS method which we recently developed to map DNA double-strand breaks genome-wide (Yan et al, Nat Commun 2017). Therefore, this is to be considered as a computational (dry-lab) position.
In addition to carrying on the aforementioned project in the Crosetto lab, the doctoral student will take part to various activities organized by the aDDRess network, and perform one or more short secondments in other network labs

Research group 
The Bienko-Crosetto Laboratory is located at SciLifeLab Stockholm (www.scilifelab.se), an interdisciplinary center for life sciences featuring state-of-the-art facilities and a broad range of groups working at the interface between biology, medicine, and computational sciences.
The main scientific interest in the Crosetto group is in understanding why certain parts of the human genome break more often than others, and how DNA transcription and 3D genome architecture influence genome fragility. In particular, we are interested in deciphering how transcription-associated DNA breaks contribute to the formation of DNA copy number alterations and other mutations associated with cancer and neurodevelopmental disorders.
The Bienko-Crosetto lab offers a highly dynamic and interdisciplinary environment where senior scientists, postdocs and students from multiple disciplines—ranging from biology, engineering, physics, and computer science—work closely together on a daily basis. The team currently features seven postdocs (molecular biology, bioinformatics, microscopy, image analysis), seven PhD students, and one lab administrator.
The successful candidate will be immersed in a thriving scientific atmosphere and have the opportunity to join the active SciLifeLab PhD community and interact with peers from three different universities (KI, KTH, SU).

The doctoral education project and the duties of the student 
In this project, the doctoral student will pursue three major tasks:

  1. Developing computational tools to study genome fragility. The student will develop a coherent and user-friendly software package to analyze BLISS data and integrate them with genome-wide data obtained with various methods such as Hi-C, ChIP-seq and RNA-seq. Furthermore, the student will implement deep learning approaches for the identification of DSB hotspots in BLISS data.
  2. Building an atlas of genome fragility in normal and cancer cells. The student will use BLISS data to build an atlas of DSBs during neuronal cell differentiation as well as organismal aging. In addition to BLISS, the student will use Hi-C and RNA-seq data to draw a comprehensive portrait of genome fragility, DNA transcription, and 3D genome architecture during these processes.
  3. Studying the relationship between genome fragility and DNA copy number alterations in cancer cells. The student will use BLISS, Hi-C, and DNA sequencing to map DSBs, chromosomal contacts, and genome structural variants in multiple cancer cell lines representative of the four major tumor types (lung, breast, colon and prostate cancer). Furthermore, the student will explore how CNAs are formed in response to topoisomerase inhibitors, by treating normal primary cells of different tissue origin with these drugs and then assessing i) the frequency of DSBs and ii) the formation of CNAs in these cells at various timepoints following drug exposure.

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.

Skills and personal qualities
Proven expertise in standard bioinformatic tools for the analysis of NGS data is mandatory (i.e., the candidate must be able to prove her/his knowledge of Bash scripting, SAMtools, BEDtools, Python including packages such as Biopython, and R including packages for DNA copy number and SNV analysis and visualization). We will prioritize candidates who have previously worked on the analysis of cancer sequencing data, and can demonstrate experience in mining large cancer genome datasets such as those from TCGA and COSMIC. In addition to proven competence with various bioinformatic tools, we require the candidate to have a solid basic knowledge in the fields of cancer genomics and genome integrity, and to be driven by fundamental biological questions rather than solely by affinity towards bioinformatic tools.

A Master Degree in Biomedicine, Biotechnology or equivalent is required. Proficiency in English equivalent to the course English B/English 6 at Swedish upper secondary school. Proficiency in the English language can be documented by an internationally recognized test such as TOEFL or IELTS, see web-link below for more information. Applicants who meet the general entry requirements (1 or 2 above) from a university in one of the Nordic countries fulfill the requirements in English. For more information regarding general and specific entry requirements: http://ki.se/en/education/entry-requirements-eligibility-for-doctoral-education

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

We are seeking for enthusiastic candidates who are truly passionate and curious about Nature, and have a keen fascination for how the genome is arranged and functions in the cell nucleus. We require candidates to have a strong motivation to work in a highly interdisciplinary and collaborative environment, and willingness to interact with scientists with computational background is mandatory.

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.

Your application should contain the following documents:

  • A personal letter and a curriculum vitae (Swedish or English)
  • Degree projects and previous publications, if any (Swedish or English)
  • Any other documentation showing the desirable skills and personal qualities described above (Swedish or English)
  • 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.

KI 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.

Type of employment Doktorandenstelle
Contract type Full time
Working hours 100%
City Solna
County Stockholms län
Country Sweden
Reference number 2-3024/2019
Contact
  • Nicola Crosetto, +46 8 524 800 00 / nicola.crosetto@ki.se
Union representative
  • Anne Edgren, OFR/S, P, O, 08-524 87570
  • Henry Wölling, SEKO, 08-524 840 80
Published 20.May.2019
Last application date 02.Jun.2019 11:59 PM CET

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