PhD Studentship: The Message in the Noise: Characterisation and Quantification of Noise in Alternative Splicing

Primary Supervisor - Dr Wilfried Haerty 

Nearly all human genes undergo alternative splicing (AS) - the process by which different transcripts are generated from a single gene. AS can generate transcripts with strikingly different functions, either due to truncation of the protein coding sequence or alteration of functional domains. AS is highly regulated during development and across tissues involved in processes such as cell differentiation, migration, and cancer.  

We have applied long-read sequencing to the study of AS across scales - from single cells to tissues - to reveal unexpected transcript diversity and have identified thousands of novel transcripts. In most cases, only one or two dominant transcripts represent the bulk of the expression arising from a gene, with the remaining transcripts lowly expressed and considered to be noise.    

The characterisation of AS diversity across cells in steady state and during differentiation can provide novel insights on the regulation of this fundamental process. More specifically, we aim to answer a) whether individual cells exhibit the same distribution of transcript expression as seen in bulk, and b) how often does functional switching - from dominant to “noisy” transcript - occur in cell differentiation?    

We offer a highly collaborative PhD project between the Haerty (bioinformatics) and Macaulay (molecular biology, technology development) groups. You will work in a rapidly developing field and gain unique expertise in experimental (cell culture, single cell biology) and computational (bioinformatics, transcriptomics, proteomic) biology.     

The project will be conducted at the Earlham Institute, a UKRI-BBSRC research centre of excellence for bioinformatics and sequencing technology development, in close collaboration with scientists at the University of Oxford, and Wellcome Trust Sanger Genome Campus. You will have access to training and career development opportunities at EI and on the Norwich Research Park as part of the Norwich Biosciences Doctoral Training Partnership.  

The Norwich Research Park Biosciences Doctoral Training Programme (NRPDTP) is offering fully funded studentships for October 2025 entry. The programme offers postgraduates the opportunity to undertake a 4-year PhD research project whilst enhancing professional development and research skills through a comprehensive training programme. You will join a vibrant community of world-leading researchers. All NRPDTP CASE students undertake a three to 18-month placement with the non-academic partner during their study. The placement offers experience designed to enhance professional development. Full support and advice will be provided by our Professional Internship team. Students with, or expecting to attain, at least an upper second-class honours degree, or equivalent, are invited to apply. 

This project has been shortlisted for funding by the NRPDTP. Shortlisted applicants will be interviewed on 28, 29 or 30 January 2025.  

Visit our website for further information on eligibility and how to apply: https://biodtp.norwichresearchpark.ac.uk/ 

Our partners value diverse and inclusive work environments that are positive and supportive. Students are selected for admission without regard to gender, marital or civil partnership status, disability, race, nationality, ethnic origin, religion or belief, sexual orientation, age or social background. 

Funding Details

Additional Funding Information 

This project is awarded with a 4-year Norwich Research Park Biosciences Doctoral Training Partnership PhD DTP studentship. The studentship includes payment of tuition fees (directly to the University), a stipend to cover living expenses (2024/5 stipend rate: £19,237), and a Research Training Support Grant of £5,000pa for each year of the studentship. 

Closing Date: 25 November 2024 (at 11.59 pm)

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