Background and aim
The centromere is a chromosomal structure serving as an anchor for the kinetochore and the mitotic spindle, which is essential for proper segregation of chromosomes during mitosis. In addition, an increasing number of studies demonstrated that centromeres have non-canonical functions in ageing or regulation of chromatin architecture (1,2).
Importantly, alterations of centromere integrity can lead to chromosome rearrangements that cause genome instability and diseases like cancer (3). Therefore, it is critical to better understand the canonical and non-canonical functions of the centromere to shed new light on mechanisms supporting normal development and human diseases.
In a recent study, we have revealed such a non-canonical function: centromeres instruct the condensation of mitotic chromosomes (4). To do this we used an assay that allows for the controlled excision of the centromere of yeast chromosome IV. At this occasion we noticed that centromere excision triggers a yet uncharacterized cellular stress response involving a severe transcriptional rewiring.
The aim of this project is to characterize the stress response that is triggered by centromere excision. By doing so, we will reveal a new physiological response to the alteration of centromere integrity.
Possible methods and techniques
- Culture and genetic engineering of the model organism Saccharomyces cerevisiae.
- Use of the centromere excision assay.
- Characterization of the response to centromere excision using PCR, qPCR, western blot, chromatin immunoprecipitation, cell fitness and growth assessment, etc.
- Classical cell biology, molecular biology and biochemistry techniques.
- In silico technics
What we offer to the student
- The student will be included as a part of the Chymkowitch research group at UiO.
- Office space and laboratory space (Fully renovated in 2021).
- An international, multidisciplinary and ambitious research group.
- Training in basic and cutting-edge techniques. Our group has broad experience in cell biology, molecular biology, biochemistry methods and statistics: Cell culture, ChIPseq, RNAseq, SLAMseq, SUMO MS, metabolomics, qPCR, immunofluorescence, microscopy, flow cytometry, Western blotting, PCR, cloning, CRISPR-Cas9, bioinformatics, stem cell technology and yeast genetics.
- Training in dissemination skills: Presentations, writing, project planning.
- Support on the way to a PhD in biology and an independent research career if applicable.
- We are an international research team (four nationalities) with researchers at different stages of their careers (Master, PhD and post-doc).
- We have weekly lab meetings/journal clubs, the research team share their expertise and support you in finding relevant literature.
- Regular social events including summer and Christmas parties as well as group retreats (depending on Covid19-related regulation).
What we expect from the student
- A highly motivated, self-driven and proactive full-time student who would like to work in an internationally competitive laboratory.
- Reading of relevant literature and spending extensive time to understand the project.
- Becoming independent in laboratory work after the relevant training periods (1-2 months), but knowing when to ask for help
- Presentation of the work during lab meetings and practice sessions for final examination.
- Writing of the Master’s thesis in collaboration with supervisors.
Supervisor for this project and the research group
Pierre Chymkowitch will be the supervisor of the student at the conceptual and strategic level and during preparation for the final examination. He is an Assoc. Professor at the Dept of Biosciences at UiO and a group leader at the Dept of Microbiology at OUS. The student and a post-doc from the group will constitute an operational subgroup in charge of this project. The post-doc will take charge of the daily supervision of the student, especially regarding lab work.
For questions and more information, please contact Pierre Chymkowitch at pierrech@ibv.uio.no
Pierre Chymkowitch web page at UiO: https://www.mn.uio.no/ibv/english/people/aca/pierrech/
Reference
- Denoth-Lippuner, A., et al., Role of SAGA in the asymmetric segregation of DNA circles during yeast ageing. Elife, 2014. 3.
- Tjong, H., et al., Population-based 3D genome structure analysis reveals driving forces in spatial genome organization. Proc Natl Acad Sci U S A, 2016. 113(12): p. E1663-72.
- Barra, V. and D. Fachinetti, The dark side of centromeres: types, causes and consequences of structural abnormalities implicating centromeric DNA. Nat Commun, 2018. 9(1): p. 4340.
- Kruitwagen, T., et al., Centromeres License the Mitotic Condensation of Yeast Chromosome Arms. Cell, 2018. 175(3): p. 780-795 e15.