Karolinska Institutet, Institutionen för fysiologi och farmakologi

At the Department of Physiology and Pharmacology we teach and conduct internationally acclaimed, high-quality research in Physiology, Pharmacology, Anesthesiology and Intensive care. We have around 400 employees, 30 research groups, and 90 doctoral students. Our research fields include cellular signaling, cardiovascular and respiratory systems, neuropsychopharmacology, neuroinflammation, pharmacogenetics, regenerative medicine, Renal System, anesthesiology and intensive care, muscle physiology and pain. Our collaboration with the clinics at Karolinska University Hospital provides unique opportunities for translational research within our subjects. More information about research at http://ki.se/fyfa_english

A doctoral position is an available doctoral education project to which a PhD student is to be recruited. After the selection process the process for admission to doctoral education will commence. An admission decision will not be taken until an individual study plan has been approved by the departmental admission board.

For more information regarding doctoral (PhD) education, see: http://www.ki.se/doctoral

Research Group

Liver function and Pharmacogenomics

Research Profile: http://ki.se/en/people/vollau

Project Title: Assessing the importance of rare genetic variants for drug response and disease

Inter-individual differences in drug response can decrease treatment efficacy or result in the manifestation of adverse drug reactions, thereby substantially contributing to patient morbidity and imposing major costs on public health care systems. Underlying these differences are physiological (gender, age, etc.), environmental (diet, co-administered medications, etc.) and genetic factors with the latter accounting for 20-30% of inter-individual differences in drug response. Recent twin studies indicated that heritable factors are responsible for 80-90% of the differences in the pharmacokinetics of certain medications; however, common genetic polymorphisms only explained less than half of this variability. These results indicate that additional factors, such as rare genetic variants are important modulators of drug pharmacokinetics. In support of this hypothesis, we previously showed that genes involved in drug absorption, distribution, metabolism and excretion (ADME) harbor vast numbers of rare genetic variants.

In the research group, we have extensive experience in population-scale pharmacogenomics and computational assessments of genetic variations. Previously, we have characterized large-scale genomic data sets and computationally analyzed the effects of rare genetic variants on pharmacokinetics on a wide range of clinically important medications. Furthermore, we have the possibility to experimentally validate promising genetic variants of interest through collaborations.

The doctoral education project and the duties of the student
The overarching objective of this project is to study the role of rare genetic variants in drug response and etiology as well as treatment of disease. Specifically, the student will work on the following projects:

  1. Optimize and integrate computational algorithms to maximize their predictive power for ADME genes
  2. Investigate the spectrum of genetic diversity in pharmacodynamic genes and analyze their importance for clinical therapeutics across individuals and ethnicities
  3. Study the panorama of rare genetic variants in human cancers and estimate their importance for treatment response
  4. Evaluate the importance and inter-ethnic variability of rare genetic factors for complex diseases, such as cardiovascular disease and schizophrenia.

This PhD project will provide the student with a deep knowledge of data analysis, computational pharmacogenomics and bioinformatics. He or she will learn to utilize in silico methods to efficiently analyze and integrate genomic sequences. Furthermore, the student will learn to translate computational findings into concrete hypotheses, thereby harnessing Next Generation Sequencing data and bridging the gap towards clinical improvements.

Entry requirements for doctoral education at KI
To be eligible for doctoral education following requirements has to be met:

General entry requirements
A person meets the general entry requirements for doctoral/third-cycle/PhD education (according to Higher Education Ordinance Chapt 7, section 39) if he/she:

  1. has been awarded advanced/second-cycle/master qualification (i.e. master degree) or
  2. has satisfied the requirements for courses comprising at least 240 credits of which at least 60 credits were awarded in the second-cycle/master level, or
  3. has acquired substantially equivalent knowledge in some other way in Sweden or abroad.

Specific entry requirements
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

Skills and personal qualities
Previous experience in pharmacogenetics and/or –genomics as well as liver biology constitutes an important merit. Furthermore, knowledge of bioinformatics tools (e.g. Python, R, Perl), pharmacology and toxicology will be an asset. Previous publications are not required but will be considered.

Assessment criteria
A selection will be made among qualified applicants on the basis of the ability to benefit from doctoral education. 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

The qualifications of the applicants will be evaluated on an overall basis.

Terms and conditions
All doctoral students at KI receive financial support during their doctoral education and employment on a doctoral studentship is the most common sort of support. During the time between recruitment and admission a short-term employment can be offered for up to 6 months.

Application process
An application must contain the following documents in Swedish or English:

  • A personal letter and curriculum vitae
  • A copy of degree certificates and associated certificates
  • A copy of degree projects and any previous publications

The application is to be submitted through the MyNetwork recruitment system.

Type of employment Doktorandplats
Contract type Full time
Reference number 2-3853/2017
  • Volker Lauschke, volker.lauschke@ki.se
Union representative
  • Bo Rydqvist, SACO, 08-524 872 67, bo.rydqvist@ki.se
  • Henry Wölling, SEKO, 08-524 840 80, henry.wolling@ki.se
  • Niklas Andersson, OFR, 08-524 874 19, niklas.andersson@ki.se
Published 28.Aug.2017
Last application date 18.Sep.2017 11:59 PM CET

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