EASTBIO: Synthetic biology-enabled new generation biosensors for alternative RNA splicing events in regulation of macrophage functions.

Alternative RNA splicing is a highly regulated process that particular exons of a gene may be included within or excluded from the final messenger RNA (mRNA) during gene expression. This greatly increases the diversity of proteins out of a relatively limited number of genes, which plays a critical role in regulation of numerous organ development and cellular differentiation processes (1). The traditional techniques to study alternative splicing including RNA sequencing and quantitative PCR to analyse alternative splicing that require RNA materials prepared from a population of cells. Therefore, the readouts are static and inter-cellular heterogeneities are averaged.
Recent studies from Dr Wang’s group (co-supervisor) has developed a novel programmable RNA sensing technology that allows efficient and specific detection of target RNA sequences in individual live cells. This project aims to harness this innovative synthetic biology approaches to develop new generation biosensors in order to reveal the dynamic regulation of alternative splicing at single cell level. Macrophages, a type of innate immune cells, will be used as the cellular model given recent discoveries of alternative splicing in regulation of their diverse functions in numerous pathophysiological processes including inflammation, infection and tissue repair and regeneration. The project is based on our prior ample experience and expertise in macrophage biology (2) and engineering of synthetic cell-based biosensors (3). Advanced signal processing and amplifying gene networks will be used within these sensor circuits to substantially boost sensitivity or trigger signalling molecules for functional studies. Together, the project will provide transformative research technologies that open up a new frontier of bioscience discovery and have significant impact in the understanding of health and diseases.
The project will provide students a comprehensive training of advanced molecular and genetic tools, innovative immunology, bioengineering and synthetic biology skills. This project will be jointly supervised by Dr Binzhi Qian at MRC Centre for Reproductive Health and Dr Baojun Wang at the Centre of Synthetic and Systems Biology giving the student a truly interdisciplinary research experience in the fields of synthetic biology and immunology.

This 4 year PhD project is part of a competition funded by EASTBIO BBSRC Doctoral Training Partnership (DTP)
EASTBIO Application and Reference Forms can be downloaded via http://www.eastscotbiodtp.ac.uk/how-apply-0 .
Please refer to UKRI website and Annex B of the UKRI Training Grant Terms and Conditions for full eligibility criteria.

Please send your completed EASTBIO Application Form along with a copy of your academic transcripts to [Email Address Removed] by the deadline.

You should also ensure that two referees send their references to [Email Address Removed] by the deadline using the EASTBIO Reference Form.