Main supervisor: Ragnhild Eskeland (IMB/CanCell)
Co-supervisor: Xuan Thang Nguyen (IMB/CanCell)
This master project is part of the Centre for Cancer Cell Reprogramming, a Norwegian Centre of Excellence at UiO (https://www.med.uio.no/cancell/english/). The centre vision is to uncover the “Achilles’ heels” of cancer and target these for reprogramming cancer cells into harmless cells.
Background
Globally, nearly 1 in 6 deaths is due to cancer (WHO, 1 February 2018). Cancer arises from the transformation of normal cells into tumour cells in a multistage process that generally progresses from a pre-cancerous lesion to a malignant tumour. These changes are the result of the interplay between a person's genetic factors, age and environmental factors (carcinogens). Epigenetic mechanisms are essential for normal development and maintenance of tissue-specific gene expression patterns in mammals. Global change in the epigenetic landscape is a hallmark of cancer.
Human sarcomas are quite rare (1% of cancers), and the driving causes of cancer remain largely unknown. Sarcoma is a cancer type that arises from transformed cells of mesenchymal origin. Thus, malignancies are made of cancellous bone, cartilage, fat, nerves, muscle, vascular, or hematopoietic tissues. Interestingly, although Sarcomas affect people of all ages, some types of sarcomas are more prominent in young adults (<35) and children. Osteo and liposarcoma are the most common malignant cancers in children and adolescents, and we will focus on this cancer in our project. The patient survival for sarcoma patients have 80% for the first five years, a number that decreases rapidly to 16% if the sarcoma has become metastatic (ACS, January 2018).
Thus, unraveling epigenetic driving mutations or alterations enabling earlier diagnosis and/or more efficient cancer treatment could result in major benefits for these patients.
Project
This master project will be a part of a larger project working on the characterization of chromatin regulatory factors altered in various types of sarcomas. The master's student will work together with a PhD student (Thang) and use various sarcoma cancer cell line models and adipose stem cells to unravel the molecular dynamics of identified epigenetic players involved in the development of sarcomas. We will perform genome-wide epigenetic analysis of the mutated/altered complexes and complementary, using various imaging and biochemical approaches, attempt to decipher the molecular dynamics of the identified complexes.
Methods
The student will learn mammalian tissue- and stem cell- culture and differentiation, various molecular and immunological methods such as cloning, transfection, CRISPR, Western blotting, chromatin immunoprecipitation, pulldown, immunofluorescence and confocal imaging. We will also perform RNA extraction, RT-PCR, and bioinformatic interpretation of data.
During this master project, you will work as a part of our Chromatin Biology group (www.chromatome.no). You will learn to make good scientific presentations, have nice creative discussions, and will be able to attend national scientific retreats as a part of a young active, ambitious research group. We collaborate with CanCell members at the Radium hospital for this project. You will be participating in all programs organised by CanCell and the master project will be at the Medical Faculty, UiO.
Reference list:
American Cancer Society (ACS), January 2018. https://www.cancer.org/soft-tissue-sarcoma
Koschmann et al., 2017, Cancer Research, 77(2); 227-33. Mutated Chromatin Regulatory Factors as Tumor Drivers in Cancer. DOI: 10.1158/0008-5472.CAN-16-2301.
Shah et al., 2014. Epigenetics and Chromatin, 7:29. A global assessment of cancer genomic alterations in epigenetic mechanisms. https://doi.org/10.1186/1756-8935-7-29.
diPietro et al., 2012, PNAS, 109(23); 9077-9082. Evidence for a functional role of epigenetically regulated midcluster HOXB genes in the development of Barrett esophagus. https://doi.org/10.1073/pnas.1116933109.
Sharma A, Akshay A, Rogne M, Eskeland R. ShinyArchR.UiO: User-friendly, integrative and open-source tool for visualisation of single-cell ATAC-seq data using ArchR. Bioinformatics. 2021 Sep 29;38(3):834–6. doi: 10.1093/bioinformatics/btab680. Epub ahead of print. PMID: 34586377.