Centromere inheritance in S. pombe and beyond
Supervisor: Dr Lakxmi Subramanian
Project description
Accurate chromosome segregation relies on the stable inheritance of functional centromeres through generations. A key determinant of centromere function is the histone H3 variant CENP-A (Centromere Protein A), that epigenetically marks and specifies active centromeres. CENP-A is highly conserved throughout evolution. Interestingly however, the factors that promote assembly of CENP-A, and the CCAN (Constitutive Centromere Associated Network) proteins that act as a scaffold linking the centromere to the kinetochore, are not fully conserved. A further layer of complexity comes from the striking differences in the cell cycle timing of CENP-A assembly in different species, with some organisms depositing CENP-A in G1 while others in G2 or S. The underlying basis for these significant evolutionary differences within the machinery that underpins chromosome segregation, which is fundamental to cell division in all eukaryotes, remains poorly understood. This PhD project will adopt synthetic and interdisciplinary approaches to carefully dissect the similarities and differences in centromeric chromatin inheritance between S. pombe and related species with regional centromeres. The project will enable us to define the composition and features of a 'Minimal Centromere' in a simple model eukaryote such as yeast.
Facilities and training
Through the course of the project, the student will gain expertise in yeast genetics, biochemistry , cell & molecular biology techniques and microscopy. He/she will have the opportunity to actively collaborate in projects within and outside the research group, both at a national and international level. The studentship also provides opportunities to develop other skills essential for career progression including but not limited to time management, project management, presentation skills and preparation of research articles.
Queen Mary University of London is a member of the Russell Group and is one of the leading research-focused institutions in the UK, with a large number of international students and staff. All PhD students and post-doctoral researchers are part of the QMUL Doctoral College, which provides support with high-quality training and career development activities. The School of Biological & Chemical Sciences offers a highly interdisciplinary research environment with state-of-the-art facilities, and is home to a number of research groups with core interests in chromosome biology and cell division. Dr. Subramanian's group offers a young, vibrant and well-funded research environment, with opportunities for networking both within and outside the institution.
Eligibility and Applying
Applications are invited from outstanding candidates who should have or, expect to receive a first or upper-second class honours degree in an area relevant to the project (e.g. Biochemistry, Genetics, Molecular/Cellular Biology, Bioinformatics). A high degree of motivation, and excellent communication and organisational skills are essential.
Interested candidates are welcome to contact Dr. Lakxmi Subramanian at l.subramanian@qmul.ac.uk. Please include your CV, motivation letter and contact details of at least two academic referees.
References
- Musacchio & Desai, A Molecular View of Kinetochore Assembly and Function. Biology 2017, 6(1)
- Drinnenberg et al., Evolutionary Turnover of Kinetochore Proteins: A Ship of Theseus? Trends in Cell Biology 2016, 26(7)
- Muller & Almouzni, Chromatin dynamics during the cell cycle at centromeres. Nature Reviews Genetics 2017, 18(3)
- Subramanian et al., Eic1 links Mis18 with the CCAN/Mis6/Ctf19 complex to promote CENP-A assembly. Open Biology 2014, 4