Stem cells have the unique capacity to develop into specialized cell types in our tissue and organ systems. They are critical for multi-cellular development, since they supply the new cells that build up our bodies as we grow and replenish, as we age, worn out, damaged, and diseased tissues. Stem cell therapies nowadays use the power of stem cells to generate treatment for medical diseases or conditions by replacing lost or damaged cells.
Tissue homeostasis and repair relies on the proper communication of stem cells and their differentiating daughter cells with the local tissue microenvironment. The fruit-fly Drosophila provides an excellent model system to study stem cell-related processes, as we can trace the fate of different cells types, manipulate genetically their function and study the effect within the wild type surrounding tissue. Due to the high degree of conservation with humans at the gene and cellular level, Drosophila has emerged as an essential partner in discoveries related to genetics, cell biology, human disease and cancer.
During Drosophila spermatogenesis, cell-cell communication is important to promote mature sperm production and give rise to fertile individuals. Germline stem cells and their daughter germ cells proliferate and progressively differentiate enclosed in squamous epithelial-type somatic cyst cells, forming a small organoid-like “cyst”, which is the functional unit of differentiation.
Research in Papagiannouli’s lab focuses on understanding how the communication between the germline and the somatic cyst cells is established and maintained, in particular how the somatic cyst cells support the developmental decision of the germline in the Drosophila testis. FP previous work has shown that cortical polarity and vesicle trafficking in the cyst cells regulates signaling with a direct impact on the germ cells they encapsulate (1). More precisely, loss of function of the highly conserved cortical polarity components Dlg, Scrib or Lgl leads to upregulation of EGFR signaling in the cyst cells, leading to germ cell death and infertility.
The aim of this project is to uncover the underlying mechanism of how cortical polarity components regulate signaling within the germline-cyst cell microenvironment. In this studenship, we will employ a highly innovative proximity biotinylation assay along with cutting-edge electron microscopy to uncover on the mechanistic level how Dlg regulates EGFR signaling in the cyst cells and dissect the basic principles of squamous epithelial cell function. Once the protein interacting networks are identified via mass spectrometry, candidate genes will be characterized using classical genetics, in gain- and loss-of function experiments, genetic interactions and RNAi knockdowns combined with immunostainings and gene expression studies.
You will be integrated in the lab of an enthusiastic young investigator who will support you to become an independent researcher and develop the skills required for your career development. This research project will provide excellent training in state-of-art Drosophila genetics, histological and molecular approaches along with innovative genomic, proteomic and a range of high-resolution microscopy techniques and image analysis tools (1, 2), to investigate key stem cell and germline organizing principles. You will be part of a dynamic working environment at Medway School of Pharmacy and the Universities of Kent and Greenwich at Medway Campus, and will have access to shared facilities such as advanced microscopy and proteomic tools. You will also work alongside our world-renowned collaborators from Stanford University and the University of Lausanne with complementing expertise.
The outcome of this research has the potential to unravel fundamental mechanisms of stem cell and germline function in tissues and organisms beyond Drosophila. Since deregulation of squamous epithelia function in humans, normally lining internal body surfaces (e.g. heart, lungs and blood vessels), leads to squamous cell carcinomas, studying their function in the relatively simple somatic cyst cells, will unravel new aspects on the underlying causes of squamous cell carcinomas. The regulatory strategies uncovered here will aid the identification of new approaches in regenerative medicine and infertility.
We look for an enthusiastic student with the ability to work both independently and as part of a team that can quickly integrate into an interdisciplinary environment. The successful candidate should have knowledge on basic molecular and protein work, however experience in confocal microscopy, immunohistochemistry, genome wide and proteomic techniques or Drosophila genetics would be an advantage. Excellent writing and communications skills in English are necessary.
Applicants should have or expect to obtain a first or upper second class honours degree (or equivalent) in an appropriate subject.
How to Apply
To apply please go to https://www.kent.ac.uk/courses/postgraduate/785/pharmacy
You will need to apply through the online application form on the main University website. Please note that you will be expected to provide personal details, education and employment history and supporting documentation (curriculum vitae, transcript of results, two academic references). You are not required to submit a research proposal.
1. F. PAPAGIANNOULI, C. W. Berry, M. T. Fuller (2019), The Dlg-module and clathrin-mediated endocytosis regulate EGFR signaling and cyst cell-germline coordination in the Drosophila testis, Stem Cell Reports, May 14, 12: 1-17 (doi.org/10.1016/j.stemcr.2019.03.008)
2. F. PAPAGIANNOULI, L. Schardt, J. Grajcarek, N. Ha, I. Lohmann (2014), The Hox gene Abd-B controls stem cell niche function in the Drosophila testis, Developmental Cell 28(2):189-202