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Deciphering the landscape of nucleoporin and lamin function in nucleocytoplasmic communication, nuclear scaffolding and transcriptional control in disease prevention


School of Pharmacy (Medway Campus)

About the Project

The nucleus has an instrumental role in cellular responses by coordinating shuttling of components in and out of the nucleus and gene expression with genome architecture and stability. At the center of key nuclear processes are the nucleoporins (NUPs), that build together the nuclear pore embedded in the nuclear envelope, and the nuclear Lamins, that constitute a filamentous network coating the inner nuclear membrane. Mutations and genetic alterations in NUPs and Lamins are linked to several human diseases and developmental defects, from autoimmune dysfunctions, muscular dystrophies and neurological diseases to cardiovascular disorders, premature aging and cancer.

The pathways leading to these diseases are multifactorial and rely on the cell-type specific role of NUPs and Lamins across different tissues and organs. The Drosophila testis, which combines a relatively simple organization with sufficient cellular complexity, allows us to investigate in vivo how nuclear processes affect the coordinated responses of the closely apposed germline and somatic lineages that are necessary to maintain testis homeostasis and fertility.

The goal of this project is to use the Drosophila testis as a model system to study the cell-type specific requirement of NUPs and Lamins in nucleo-cytoplasmic communication, transcriptional activation, scaffolding and nuclear compartmentation. More precisely, this project aims to:

• uncover the mechanistic features of NUP and Lamin function in a lineage-specific way using cutting-edge proteomic and genomic tools.
• elucidate how signaling pathways intersect with NUP and Lamin function to promote soma-germline communication and co-differentiation using advanced genetic and high-resolution microscopy techniques.
• transfer the findings from Drosophila to the mouse model and formulate testable rules and universal regulatory strategies to eventually translate in the context of human physiology and diseases.
Uncovering the divergent functions of NUPs and Lamins in nuclear transport, gene regulation and scaffolding will impact the efforts in tackling disease-causing mutations and developing new therapeutic approaches for cancer, infertility, ageing and regenerative medicine.

You will

• join the lab of an enthusiastic investigator who will support you develop the skills required for your career development.
• embark on a research project that will provide excellent training in state-of-art genetic, histological and molecular approaches along with innovative genomic, proteomic and advanced microscopy tools.
• become part of a dynamic academic community at Medway School of Pharmacy and the Universities of Kent and Greenwich at Medway Campus.
• gain access to excellent state-of-the-art research facilities at MSoP and Medway campus
• work alongside our UK and international collaborators from Stanford University and the University of Lausanne, with complementary expertise.

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 is expected to have knowledge on basic molecular and protein techniques. Experience in confocal microscopy, immunohistochemistry, genomic and proteomic techniques or Drosophila genetics would be considered an advantage. Excellent writing and communications skills in English are necessary.

More information about the lab is available on our webpage: https://www.msp.ac.uk/person/fani-papagiannouli/#teaching
For more information about the post and the project please contact directly Dr. Fani Papagiannouli ().

As an equal opportunities institution we welcome applicants from all sections of the community regardless of gender, ethnicity, disability, sexual orientation and transgender status. All appointments are made on merit.

Entry requirements:

Applicants should have or expect to obtain a first or upper second class honours degree (or equivalent) in an appropriate subject and a Masters (at Merit or above) in Biological Sciences, Pharmaceutical Science or closely related subject.

How to Apply:

To apply please go to https://msp.ac.uk/postgraduate/?course_id=785&course_level=postgraduate

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

We welcome applications from people with disabilities and Black, Asian and Minority Ethnic (BAME) backgrounds.

Funding Notes

This project is a self-funded opportunity available to both Home/EU and International students.

Applicant must have access to funding to cover tuition fees, living costs and any related project costs (i.e. bench fees).

Applicants who have access to international scholarship applications, please contact directly Dr. Fani Papagiannouli.

References

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: 10.1016/j.stemcr.2019.03.008)

2. F. PAPAGIANNOULI*, M. T. Fuller, I. Lohmann (2018), Nuclear export in somatic cyst cells controls cyst cell-germline coordination and germline differentiation in the Drosophila testis, bioRxiv Oct. 24 (doi: 10.1101/452466)

3. 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 (doi: 10.1016/j.devcel.2013.12.016)

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