PhD Studentship –The genetics and developmental biology of cell division in mammary stem cells
PhD Supervisor: Dr Salah Elias co supervisor: Prof. Keith Jones
Application Deadline: 17 March 2017
Interviews will be held in early April 2017
PhD Description:
Despite recent advances in the treatment of breast cancer, disease recurrence involving tumorigenic mammary stem cells (MaSCs) remains a major obstacle to therapies. MaSCs display potent regenerative properties and undergo asymmetric cell divisions (ACDs) to balance self-renewal and differentiation programmes during development and homeostasis. However, the mechanisms controlling the division modes in mitotic MaSCs, and how this influences epithelial differentiation and architecture remain poorly understood. There is increasing evidence, linking perturbations in ACDs in MaSCs to tumorigenesis (1). Uncovering the molecular mechanisms modulating oriented cell divisions in MaSCs is essential not only for advancing our understanding of normal tissue biology, but also for elucidating how an imbalance in self-renewal and differentiation can contribute to the abnormal stem cell behaviour and tissue architecture observed in breast cancer.
We recently identified a common microtubule-based trafficking mechanism that governs oriented cell divisions and polarity in stem and progenitor cells in the developing mammary gland (2, 3). We identified a critical developmental window, where stem cell divisions switch from symmetric to asymmetric modes to promote differentiation. The goal of the PhD project is to investigate the roles that microtubule-based trafficking mechanisms play in ACDs and identify novel mechanisms that couple apical cell polarity and spindle orientation machineries; identify the factors that dictate whether a given MaSC divides symmetrically or asymmetrically and determine how this influences epithelial differentiation and architecture; and characterise the cell fate determinants that are segregated during ACDs. To conduct this exciting project, the PhD student will be trained in a range of powerful technologies including in vivo single-cell lineage tracing of MaSCs, 3D organoids, and high-resolution 3D imaging techniques. He/she will be actively involved in developing genome editing approaches (e.g. CRISPR), and bioinformatics tools to integrate and analyse large data sets generated from other experimental approaches including proteomics and next generation sequencing.
1. Faraldo M.M. & Glukhova M.A. (2015). Regulating the regulator: Numb acts upstream of p53 to control mammary stem and progenitor cell. The Journal of Cell Biology 211, 737-739.
2. Elias S. et al. (2015). Huntingtin Is Required for Epithelial Polarity through RAB11A-Mediated Apical Trafficking of PAR3-aPKC. PLoS Biology 13, e1002142.
3. Elias S. et al. (2014). Huntingtin Regulates Mammary Stem Cell Division and Differentiation. Stem Cell Reports 2, 491-506.
Training and Development Opportunities:
The Centre for Biological Sciences offers a unique and exciting collaborative research environment and will provide the PhD student with support, mentoring, training and development opportunities. He/she will have full access to state-of-the-art research facilities (including animal, imaging, flow cytometry, proteomics, genomics, histology and tissue culture), and benefit from training for the use of equipment as well as for data processing and analysis. The PhD student will be given opportunities to present the results of the project at major national and international conferences.
Knowledge, Skills and Experience Needed for the Position:
Successful candidates are expected to be highly motivated, enthusiastic and have an outstanding academic track record. Applicants must have at least an upper second class degree or Masters degree in Biological Sciences or related fields.
Previous experience in cell and molecular biology, mouse genetics and advanced imaging techniques is desirable. Experience/understanding of construct design in genome editing, computational modelling and/or bioinformatics tools is a plus. A strong interest and ability to acquire new skills and work independently and collaboratively, as part of a research team, is absolutely essential. The PhD student must be an effective communicator with an ability to present his/her work both within the laboratory and to others in the field.
Funding Notes:
The project is funded for 3 years and welcomes applicants from the UK and EU who have or expect to obtain at least an upper second class degree in Biological Sciences or allied subjects.Funding will cover fees and a stipend at current research council rates of £14,553 per annum 2017/18 entrants.
Due to funding restrictions this position is only open to UK/EU applicants
Application Procedure:
Applications for Biological Sciences should be submitted online at:
https://studentrecords.soton.ac.uk/BNNRPROD/bzsksrch.P_Login?pos=4973&majr=4973&term=201718Please place Salah Elias’ name in the field for proposed supervisor.
General enquiries should be made to Dr Salah Elias at S.K.Elias@soton.ac.uk
Any queries on the application process should be made to pgafnes@soton.ac.uk
Applications will be considered in the order that they are received, and the position will be considered filled when a suitable candidate has been identified.
The University of Southampton and Biological Sciences both hold an Athena Swan Silver & Bronze Award, respectively, demonstrating their commitment to provide equal opportunities and to advance the representation of women in STEM/M subjects: science, technology, engineering, mathematics and medicine. Due consideration will be given to applicants who have taken a career break. University benefits include onsite childcare facilities, state-of-the-art on-campus sports, arts and culture facilities, a full programme of events and a range of staff discounts.
Closing Date: 17 Mar 2017
Post Type: PhD Studentship (Funded)