Background and aim
Obesity is a serious global health problem that increases the risk for type 2 diabetes and other related diseases like cancer. Unfortunately, current treatments often result in metabolism damage without inducing weight loss. There is thus a clear need for antiobese drugs that improve metabolism and induce weight loss. To fulfill this need, we must gather more information about the molecular mechanisms involved in adipose tissue formation and biology.
Our group is investigating the regulation of gene expression by the small ubiquitin-like modifier SUMO during the course of cellular differentiation (more info about SUMO available in this review: (1). We have found in mouse cellular systems that chromatin-bound SUMO supports transcription during adipocyte differentiation (1). In addition, we have preliminary data suggesting that adipocyte identity and metabolism are regulated by SUMO.
In this project we aim at validating these findings in human cells. To do so, we have access to a biobank of human adipose tissue samples from healthy and obese donors from which will purify human adipose stem cells (hASCs). We will use small-molecule sumoylation inhibitors to address specific aspects of the role of SUMO-regulated gene control, -cell identity and -metabolism in differentiating and mature hASCs.
Possible methods and techniques
- Participation to the establishment and procedures of the operative loop that is required to collect and store hASCs from donors in our biobank. This loop will involve clinicians at Aker Hospital’s, the group of Prof. Bente Halvosen (Oslo University Hospital, OUS) and our group (UiO and OUS).
- Purification, amplification and culture of hASCs from donors.
- Use of hASCs from donors to address the effect of small molecule sumoylation inhibitors on adipocyte differentiation and metabolism using confocal microscopy, qPCR, western blot, ChIP, 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.
- 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 Chymkowitchwill 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 will be integrated in a subgroup composed of a Post-doc and a PhD student who will be in charge of daily supervision, 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
- Chymkowitch, P., P.A. Nguea, and J.M. Enserink, SUMO-regulated transcription: challenging the dogma. Bioessays, 2015. 37(10): p. 1095-105.
- Zhao, X., et al., Waves of sumoylation support transcription dynamics during adipocyte differentiation. bioRxiv, 2021: p. 2021.02.20.432084.