Deciphering the role of alternative splicing in protein synthesis

A vast majority of genes in our genome undergo alternative splicing, a fundamental process in gene regulation, leading to the production of multiple protein isoforms from a single gene. This process can significantly impact protein function and range of cellular processes. However, our understanding of how alternative splicing of genes encoding ribosomal proteins affects ribosome composition and function remains limited. Exploring these splice variants could reveal new insights into the regulation of protein synthesis and potential implications for diseases linked to ribosomal and splicing abnormalities. In this PhD project, you will explore ribosomal gene isoforms, characterize their functional roles, and investigate their impact on protein synthesis. You will have opportunities to work with molecular cloning, CRISPR-based isoform editing, RNA sequencing and functional assays to elucidate the biological significance of these splice variants. The findings could contribute to a deeper and newer understanding of the complexity of protein synthesis regulation.

Approximately 95% of multi-exon genes in the mammalian genome undergo alternative splicing, significantly contributing to proteome diversity and functional complexity. Several transcriptomics atlas initiatives reveal the existence of multiple splice variants for a single gene in different cell types of an organ. However, the functional significance of splice variants remains poorly understood. Particularly, the understanding and characterisation of splice variants encoding ribosomal proteins remain rather poor. This knowledge is essential to unveil the nuanced mechanisms of protein synthesis and how different splice variants might contribute to cellular function and adaptability. Further, it could provide insights into the regulation of gene expression and potential implications for diseases linked to splicing and ribosomal abnormalities.

In this PhD project, we will be addressing fundamental questions to understand the complexity of protein synthesis driven by alternative splicing of ribosomal genes. Following broad objectives will be addressed: (i) Identify and catalogue the splice variants of ribosomal genes in different cell types (ii) Reveal the regulatory proteins involved in the alternative splicing of ribosomal genes and their cell-type specificity (iii) Determine the functional role of these splice variants in protein synthesis. Overall, this project seeks to understand the fundamental and heterogenous nature of protein synthesis machinery. You will have opportunity to work with human and mouse cell models using cutting edge technologies such as CRISPR-based splice editing, molecular cloning, cell reprogramming and RNA-sequencing. You will learn several complementary skills such as single cell sequencing and analysis of big data. There will be opportunities to collaborate with leading experts in the field and present your findings at international meetings. Potential candidates should have an interest in cell biology and a passion to pursue a research project. A background in cell and molecular biology, including neurobiology, biochemistry or genetics is advantageous but not necessary. Having computational skills are also an added advantage. All necessary training will be provided and the most important criteria for a successful candidate is passion and interest for the project.

This project will be hosted within the School of Biological Sciences (SOBS) at the University of Southampton. The University of Southampton is a research-intensive university and a founding member of the Russell Group.

If you are interested, and would like to chat informally before officially applying, please email Dr. Kif Liakath-Ali (kif.liakath-ali@soton.ac.uk) with your CV. In your email, please include 1-2 paragraphs about yourself, your experience, and your interests, specifically on the advertised project. For more information about the lab and the supervisor, please visit http://www.splicelab.co.uk.

Entry Requirements

A UK 2:1 honours degree, or its international equivalent. For international applicants, an IELTS overall score of 6.5 or above is required.

How To Apply

Include:

·      the project reference number

·      any documents someone would need to supply (CV, references, degree transcripts)

·      any other details someone would need once they begin the application process

First, please email Dr. Kif Liakath-Ali (kif.liakath-ali@soton.ac.uk) with your CV. In your email, please include 1-2 paragraphs about yourself, your previous and current work/science experience, and your scientific interests.

For the actual application, please provide:

(i) CV and a letter of interest explaining why you are interested in this project

(ii) 2 reference letters (candidates should arrange the letters sent directly to kif.liakath-ali@soton.ac.uk by their referees)

(iii) degree transcripts to date (for international applicants, translations must be provided by official translators),

(iv) proof of English proficiency (only for international students)

If interested, contact Dr Kif Liakath-Ali (kif.liakath-ali@soton.ac.uk) for an initial conversation.

www.splicelab.co.uk

https://www.southampton.ac.uk/people/doctor-kif-liakath-ali/