Alternative splicing regulation at the single cell resolution: Protocols and computational developments for long read RNA-Seq in single cell
Applications are open for this LongTREC PhD project in the Wilfried Haerty Group at the Earlham Institute.
LongTREC is a Doctoral Network of the Marie Sklodowska-Curie action program (MSCA-DN) that will develop methods and tools for the analysis of transcriptomic data obtained with the most recent single-molecule, long-reads sequencing technologies.
Nearly 95% of multiexonic genes in humans undergo alternative splicing, the process by which multiple isoforms are transcribed from a single gene through differential inclusion of exons and splice sites.
Alternative splicing is a highly regulated process with evidence for the developmental stage-, tissue-, and cell-specific isoforms. The development of long-read RNA sequencing has opened the unique opportunity to gather a much more comprehensive understanding of the existing transcript diversity and its regulation. Work by ourselves and others, mainly conducted at the tissue level demonstrated that the current transcript diversity in human is severely underestimated.
Although already extremely informative, this work was conducted on thousands to millions of cells, obfuscating transcripts that are found in specific cell types including rare cell types such as stem cells. Recent molecular developments by ourselves and others aiming to bring long-read sequencing to single cells already provided unique insights on transcript regulation but also fundamental events such as VDJ recombination. Methods so far have been suffering from relatively low throughput leading to the recovery of genes with mid to high expression. Additionally, there is limited availability of computational tools for their analysis and visualization.
We offer a highly collaborative PhD project between the Haerty (bioinformatics) Macaulay (molecular biology, technology development) groups. The main aim of the project is to develop protocols and computational solutions to further enable the applications of long-read RNA sequencing to single cells, with a specific focus on rare cell types such as hematopoietic stem cells, and genes fundamental to our physiology and of primary interest in disorders and diseases but expressed at low levels.
The student will work in a rapidly developing field and gain unique expertise in computational biology, large dataset analysis, genomics, transcriptomics, sequencing technologies, molecular biology, technology development, and therapeutic target identification.
The project will be conducted at the Earlham Institute, a UKRI-BBSRC strategically supported research centre of excellence for bioinformatics and sequencing technology development. In addition to the training offered through the LongTrec network, the student will have access to training and career development opportunities at EI and on Norwich Research Park.
We welcome applications from PhD candidates from any country fulfilling the following criteria:
- Eligible candidates must not have resided or carried out their main activity (work, studies, etc.) in the country of their host institution for more than 12 months in the 3 years immediately prior to their recruitment by the host institution (i.e. the starting date indicated in the employment contract/equivalent direct contract).
- Eligible candidates shall at the date of recruitment by the host institution (i.e. the starting date indicated in the employment contract/equivalent direct contract), be in the first 4 years (full-time equivalent research experience) of their research careers and not have been awarded a doctoral degree.
- Eligible candidates must hold an undergraduate degree (2:1 equivalent) or a Master's degree in biology, biotechnology, or molecular biology by June 2023 or an equivalent experience, or must hold an official university qualification from a country of the European Higher Education Area with a minimum of 300 ECTs of official university studies.
- Eligible candidates should have experience in wet lab.
- In all cases, employment will be conditioned to acceptance by the Doctoral school of the associated PhD awarding institution.
- Successful candidates must have a high level of proficiency in written and spoken English, which will be assessed with the motivation letter and the interview, respectively.
Application and selection process
Applications must contain the following documents (in pdf):
- a CV (including publications, if any),
- a motivation letter,
- 2 reference letters,
- Statement in diversity, inclusion, and sustainability,
- Copies of Bachelor's and Master's degree certificates. Candidates should include the transcripts in English of academic records for the studies that make them eligible for a doctoral program. If these studies have been completed by the deadline for applications, the total number of credits for the degree and the credits awarded must also appear.
Our work is primarily computational, focusing on comparative genomics and population genetics, as well as data integration, approaches to identify putative functional elements, characterise their evolution and assess the potential impact of their disruption.