There is more than meet the eye: reconstruction of isoform level regulatory networks in the human brain

Nearly all of human genes underdo alternative splicing (AS) the process by which different transcripts are generated from a single gene, 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 being 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 identifying 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 if individual cells exhibit the same distribution of transcript expression as seen in bulk and 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) Macaulay (molecular biology, technology development). The student will work in a rapidly developing field and gain unique expertise in experimental (cell culture, single cell biology) and computational (bioinformatics, transcriptomics, proteomic) biology.