Postdoctoral Researcher in Chromosome Biology: Functional and molecular characterization of topoisomerase regulatory interactions during transcription.
We are looking for an ambitious, highly motivated and curious Postdoctoral Fellow candidate to join Laura Baranello’s research group at the Karolinska Institute in Stockholm, Sweden, to elucidate the mechanism of topoisomerase regulation during transcription with the overall goal to develop new strategies to inhibit topoisomerases function for cancer treatment.
Laura Baranello, Ph.D., was recently recruited from the National Cancer Institute, National Institutes of Health (NCI, NIH, USA) to the Department of Cell and Molecular Biology of Karolinska Institutet as an Assistant Professor. Her group focuses on understanding how transcription, chromatin and DNA topology are functionally coordinated in human cells. The detailed understanding of topoisomerase regulatory networks during transcription will provide a new rational to target topoisomerases in cancer therapy. The group is also associated to the laboratory of David Levens at the NCI (NIH, USA). The successful applicant will thus be part of a network of recognized scientists, will have the possibility to spend some time at the NIH and have access to state-of-the-art technologies and facilities. More information about the activities of Laura Baranello’s group can be found here: http://ki.se/en/cmb/laura-baranellos-group
Topoisomerases (Top1 and Top2) are essential enzymes that regulate the topology of DNA favoring DNA replication and transcription by cleaving and resealing DNA strands. Because cancer cells have higher rates of replication and global transcription 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.
We have recently shown that topoisomerases execute their function through regulatory interactions with molecular partners that modulate their activity to affect the expression of key genes. Interfering with these regulatory interactions, instead of blocking topoisomerase activity directly, could provide a new strategy for cancer treatment with lower off-target toxicity compared to currently available topoisomease inhibhithors (Baranello et al., Cell 2016).
This interdisciplinary research project aims to define the mechanism of topoisomerase regulation by different protein partners during transcription and other DNA transactions. We will use a combination of biochemical assays, next-generation sequencing, CRISPR-based genome editing and bioinformatics approaches to define topoisomerase site of activity across the human genome, reveal new factors regulating topoisomerase, decipher their mechanisms of topoisomerase regulation and identify strategies to target topoisomerase functional interactions in cancer cells.
We are looking for an enthusiastic and highly dynamic candidate with a Ph.D. in molecular biology or related sciences and a strong track record. The ideal candidate is expected to lead the project in collaboration with the PI and other team members, supervise students and participate in common laboratory duties. The successful candidate should have excellent interpersonal and organization skills, communicate well and work in a team. A strong background in chromatin biology, expertise in standard biochemistry and molecular biology techniques as well as a good knowledge of both spoken and written English are required. Experience with next-generation sequencing techniques, high-throughput drug screening and with large-scale bioinformatics analysis will be considered a plus.
The initial scholarship is available within a 4-year period from the receipt of the doctoral degree for maximum 24 months, with a 12 months trial period. Depending on the scientific progress there is possibility for extension.
Applications will be screened continuously and a decision will be made as soon as we will find the right candidate.
An application must contain the following documents in English:
1. A complete Curriculum vitae, including date of Ph.D. thesis defense, title of the Ph.D. thesis, previous academic positions, academic title, current positions, academic distinctions and committee work.
2. A complete list of publications.
3. Contact information of two references.
4. A brief motivation letter stating the reason why the candidate is interested in this project (no more than half a page, font 12).
5. A summary of past and current work (no more than half a page, font 12).
Baranello L, et al. RNA Polymerase II Regulates Topoisomerase 1 Activity to Favor Efficient Transcription. Cell, 2016 Apr 7; 165 (2) :357-71. Kouzine F, Gupta A, Baranello L, et al. Transcription-dependent dynamic supercoiling is a short-range genomic force. Nat. Struct. Mol. Biol. 2013 Mar;20(3):396-403.