About the position
This is a new post funded through the Knut and Alice Wallenberg Stiftelsen, based within the Department of Medicine Huddinge. The project is focused on single cell analysis and modeling of normal and malignant hematopoiesis. The postholder will report directly to the Principal Investigator, Professor Sten Eirik Jacobsen (http://ki.se/en/medh/sten-eirik-w-jacobsen-group).
This is an exciting position that allows the postholder to apply a variety of statistical and computational techniques to analyze and interpret a wide range of genomic data sets, from single-cell RNA-seq to the correlation of whole genome sequencing data with clinical outcome in patient cohorts. There is scope for developing novel analysis methods in collaboration with scientists at Karolinska Institutet, as well as together with external collaborators.
About The Jacobsen lab
The Jacobsen lab comprises an international collaborative team focused on understanding at the single cell level the cellular and molecular pathways governing the earliest fate decisions in normal hematopoiesis [1-4] and how these are dysregulated in hematologic malignancies [5-9]. This is studied in mouse models, as well as in relevant patients. Key technologies applied towards these research questions include high-throughput DNA and RNA sequencing including single cell analysis, genetic fate-mapping using next-generation-sequencing technology, flow cytometry, mouse genetics and various in vitro and in vivo stem cell assays. The postholder will have the opportunity to lead projects focused on the analysis of single-cell RNA-seq data to understand heterogeneity of normal and leukemic hematopoietic stem and progenitor cells (e.g. see our recent paper in Nature Medicine ), as well as generate testable models from single cell hematopoietic stem cell functional data (e.g. see our recent paper in Nature ).
Projects will be pursued in part at the Center for Hematology and Regenerative Medicine (HERM; http://ki.se/en/medh/herm), and in part at the Department of Cell and Molecular Biology (CMB; http://ki.se/en/cmb/startpage). The Jacobsen lab also has close interactions with world leading research groups, and the recruited bioinformatician will benefit from interactions in this collaborative network. Of particular relevance, the bioinformatician will interact closely with the Professor Seishi Ogawa, a world leader on next-generation sequencing of cancer [11, 12], and a guest professor at the Karolinska Institute, as well as Assistant Professor Petter Woll, a group leader at the Karolinska Institute focused on studies of normal and malignant hematopoiesis and a close collaborator of Professor Jacobsen [2, 8, 9]. A key focus will be to apply up-to-date statistical and computational methods to unravel important biological questions, specifically analysing and integrating large-scale single cell sequencing, cell biology and clinical data sets. The candidate will have access to state-of-the-art computational tools available through the Swedish National Infrastructure for Computing (SNIC) and Uppsala Multidisiplinary Center for Advanced Computational Science (UPPMAX) providing large scale high performance computing resources, storage capacity and advanced user support (https://www.uppmax.uu.se). The successful candidate must demonstrate excellent statistical and programming skills with the ability to manage simultaneous projects to meet deadlines.
Duties in bold will be contingent on the candidates qualifications.
- Lead project focused on computational modelling and analysis of normal and malignant hematopoiesis, independently or in collaboration with wet lab scientists in the lab.
- Analyse and interpret large single-cell DNA and RNA sequencing datasets.
- Analyse and interpret data from large scale sequencing projects including population-based RNA-sequencing, whole genome sequencing, exome sequencing, ChIP-Sequencing, and directed sequencing using site target amplification.
- Advise and supervise biostatistical and laboratory staff on a day-to-day basis on statistical methods and experimental design for projects.
- Identify, define and plan new projects which contribute to the overall aims of studies and clinical trials including providing bioinformatics input into outline and full grant proposals, including as a co-applicant.
- Contribute to the overall planning of studies.
- Identify and troubleshoot technical or scientific problems, working collaboratively with database experts and scientific programmers.
- Develop methodologies for analysis and data collection in collaboration with members of the research team, and where appropriate to develop novel statistical and computational methodologies and techniques.
- Manage multiple simultaneous projects, meeting deadlines as required.
- Design, construct and maintain databases relevant to the work of the team/laboratory, for example, relating to integration of clinical and genetic data on patient cohorts.
- Proactively collaborate and develop research activities with external groups both within the Karolinska Institutet and elsewhere.
- Contribute to the production of scientific reports and publications for high profile journals, including taking leadership in more specialized publications on novel aspects of bioinformatics.
- Keep detailed, accurate and comprehensible records of work performed and communicate developments and results to colleagues on a regular basis, as required.
- Communicate and meet with the group leaders on a regular basis and with external collaborators as the need arises.
- Regularly present data at laboratory meetings
- Clearly present at scientific meetings, and to undertake further training as appropriate.
- Maintain confidentiality regarding research data when interacting with non-collaborating researchers.
- Work as part of a team and independently as required, organizing work efficiently, prioritising workload and taking personal responsibility for assigned tasks.
- A PhD or MSc in computational biology, bioinformatics, statistics or a similar scientific subject, with post-qualification research experience.
- Demonstrable skills and a track record in computational biology, bioinformatics or statistics.
- Excellent organisational/planning skills with the ability to manage projects and achieve deadlines.
- Excellent communication skills, both oral and in writing to be able to liaise and explain statistical/computational concepts to bioinformaticians, clinicians and researchers from many disciplines at all levels of seniority.
- The ability to work as part of a team as well as independently.
- Good publication record in high-impact peer reviewed journals.
- Experience in analysis of high dimensional datasets.
- Experience in interpretation, visualization and presentation of complex data sets.
- Experience of working in a UNIX/LINUX environment.
- Demonstrable programming language experience (such as C++, Java, or Python) and statistical programming in R.
- Experience of analysis of single cell genomics data.
- Experience of R/Bioconductor plus other analysis packages.
- Experience of sequencing data analysis pipeline development.
- Knowledge of hematopoiesis biology.
- Database interrogation and/or programming (SQL).
- Experience in using a high performance computing cluster.
- Experience with human genomics databases (including Ensembl, NCBI, UCSC, HapMap, GEO, ArrayExpress, 1000 genomes).
An employment application must contain the following documents in English or Swedish:
- A maximum one page cover letter summarizing previous experience, research interest and motivation for position
- A complete curriculum vitae of current work and work history
- A complete list of publications
- Names and contact details of three references who are familiar with the applicant’s recent research and training
The application is to be submitted on the Varbi recruitment system.
- Boiers, C., et al., Lymphomyeloid contribution of an immune-restricted progenitor emerging prior to definitive hematopoietic stem cells. Cell Stem Cell, 2013. 13(5): p. 535-48.
- Carrelha, J., et al., Hierarchically related lineage-restricted fates of multipotent haematopoietic stem cells. Nature, 2018. 554(7690): p. 106-111.
- Luis, T.C., et al., Initial seeding of the embryonic thymus by immune-restricted lympho-myeloid progenitors. Nat Immunol, 2016. 17(12): p. 1424-1435.
- Sanjuan-Pla, A., et al., Platelet-biased stem cells reside at the apex of the haematopoietic stem-cell hierarchy. Nature, 2013. 502(7470): p. 232-6.
- Booth, C.A.G., et al., Ezh2 and Runx1 Mutations Collaborate to Initiate Lympho-Myeloid Leukemia in Early Thymic Progenitors. Cancer Cell, 2018. 33(2): p. 274-291 e8.
- Giustacchini, A., et al., Single-cell transcriptomics uncovers distinct molecular signatures of stem cells in chronic myeloid leukemia. Nat Med, 2017.
- Mead, A.J., et al., Impact of isolated germline JAK2V617I mutation on human hematopoiesis. Blood, 2013. 121(20): p. 4156-65.
- Tehranchi, R., et al., Persistent malignant stem cells in del(5q) myelodysplasia in remission. N Engl J Med, 2010. 363(11): p. 1025-37.
- Woll, P.S., et al., Myelodysplastic syndromes are propagated by rare and distinct human cancer stem cells in vivo. Cancer Cell, 2014. 25(6): p. 794-808.
- Giustacchini, A., et al., Single-cell transcriptomics uncovers distinct molecular signatures of stem cells in chronic myeloid leukemia. Nat Med, 2017. 23(6): p. 692-702.
- Suzuki, H., et al., Mutational landscape and clonal architecture in grade II and III gliomas. Nat Genet, 2015. 47(5): p. 458-68.
- Yoshida, K., et al., Frequent pathway mutations of splicing machinery in myelodysplasia. Nature, 2011. 478(7367): p. 64-69.
Karolinska Institutet is one of the world’s leading medical universities. Its vision is to significantly contribute to the improvement of human health. Karolinska Institutet accounts for the single largest share of all academic medical research conducted in Sweden and offers the country’s broadest range of education in medicine and health sciences. The Nobel Assembly at Karolinska Institutet selects the Nobel laureates in Physiology or Medicine.
Pursuant to the regulations of the Swedish National Archives, applications are kept on file for two years after the appointment has gained legal force. The regulations do not apply to attachments that have been printed or otherwise published.
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