Postdoctoral position in computational structural screening of genetic variants between a bioinformatics group and a clinical genetics lab

Departments of Oncology-Pathology and Molecular Medicine and Surgery

Do you want to contribute to top quality medical research?

Karolinska Institute aims to be a pioneering university. As part of this ambition, in 2022 it created the KI Research Incubator (KIRI), a dynamic environment for top junior researchers, with the aim to strengthen innovative and interdisciplinary collaborations and promote ground-breaking research through its KIRI postdoctoral programme. This postdoctoral position is funded through one of the first selected KIRI interdisciplinary projects “Connecting biological scales – atomic-level interpretation genetic variants in rare diseases”, a collaboration between KIRI fellows Prof. Laura Orellana, who leads the “Protein Dynamics and Mutation” molecular modelling group, and Prof. Giedre Grigelioniene, PI of skeletal dysplasia research team in Clinical Genetics group focused on the identification of new genetic variants associated with rare skeletal malformation syndromes.

Your mission

Your main role will be to develop a computational pipeline to perform a broad range of multiscale computational analyses of potential disease-causing variants, focusing on a clinically curated benchmark of approximately 100 genes related to skeletal dysplasia. The main goal will be to develop new pathogenicity scores for variant classification including dynamical information from coarse-grained and atomistic simulations and potentially also protein-protein and protein-nucleic acid interactions. As a more senior member in a crossroad between two growing research groups, you will have the chance to play a bigger leadership role and mentor MSc and doctoral students, while also benefiting from direct supervision and collaboration from two PI, one who is experienced in structural computational biology and another who has a long clinical and research experience in rare genetic disorders and new gene discoveries. You will have the opportunity to work with significant freedom and independence within an extremely interdisciplinary as well as an international setting. This position is for two years.

Your profile

We are looking for a highly motivated postdoctoral researcher with broad experience in structural bioinformatics and biomolecular modelling. The candidate is expected to participate in collaborative efforts to develop a workflow for multiscale screening of human mutations, integrating different coarse-grained and atomistic simulation methods. The candidate will hold a shared position between Prof. Orellana “Protein Dynamics and Mutation” lab, focused on the development of biophysical modelling methods with a focus on disease mutations, and Prof. Grigelioniene translational research team, focused on the identification and validation of new genetic variants associated to rare skeletal diseases. He/She will work developing a general computational pipeline for variant clinical scoring, also contributing to modelling and interpretation of selected new variants discovered by Prof. Grigelioniene’s team, which can be potentially validated experimentally. Ideally, the pipeline will be the basis for a database/server to facilitate the interpretation of new variants by clinicians.

Advanced knowledge in structural bioinformatics and broad proven experience with molecular simulation packages (GROMACS, AMBER, etc) and knowledge of common analysis techniques (Network Analysis, PCA, etc) are prerequisites; ideally, the applicant will also have at least familiarity with some coarse-grained method (MARTINI simulations, NMA, etc). The applicant must have strong skills in programming languages used in the biomolecular simulation field. Previous experience with the evaluation and/or structural interpretation of mutations and developing web applications will be highly valued; additional knowledge of other molecular modelling methods such as molecular docking, virtual screening, homology modelling, etc or machine learning applications will be also appreciated.
Fluency in English, a high level of organizational and communication skills, as well as an ability to work independently, is mandatory. The candidate is also expected to take a strong lead in managing project(s), contribute to writing manuscripts and grants, and train and mentor junior members of the team.

To be eligible for employment as a postdoctor a doctoral degree or a foreign degree deemed to be equivalent to a doctoral degree is required. This eligibility requirement must be fulfilled at the latest at the time of the employment decision. It is considered as an advantage if you have completed your doctoral degree within the last three years, if there are special reasons, your degree may have been completed earlier.

What do we offer?

An exceptionally interdisciplinary position, between a clinical genetics team and a computational-structural group, that develops advanced biophysical modelling methods and integrates them with cryo-EM and experiments in-house and through a wide national and international collaborative network
Karolinska Institute is one of the world's leading medical universities, and responsible to award the Nobel Prize in Medicine. A creative and inspiring environment full of expertise and curiosity, with top-level infrastructure for life sciences
Karolinska Institute is a public university, which entitles employees to several social benefits, access to sports facilities for free and reimbursements for medical care.

See Prof. Orellana’s lab page for more information and selected publications:
Laura Orellanas group

Prof Grigelionienes page for more information and selected publications:
Giedre Grigelioniene

Location: Solna

Application

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

A cover letter, explaining your background, research interests and motivation to join
A complete resumé, including date of the thesis defence, title of the thesis, previous academic positions, academic title, current position, academic distinctions, and committee work
A complete list of publications
A summary of current work (no more than one page)

Welcome to apply at the latest March 15th, 2023

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

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