PhD Studentship: Functional interpretation of human NF1 genetic variation using precision genome editing and in vivo phenotyping

Overview

This PhD studentship investigates the functional interpretation of human neurofibromatosis type 1 genetic variation using precision genome editing and in vivo phenotyping. Neurofibromatosis type 1 is a multisystem genetic disorder caused by mutations in the NF1 gene affecting roughly 1 in 3,000 people, leading to symptoms such as skin pigmentation abnormalities, circulatory system issues, and nerve tumours causing chronic pain and movement problems. The research aims to connect human genetic variants, molecular functions, and organismal phenotypes by combining data science, cell biology, and developmental biology.

What you get

The studentship provides funding for tuition fees and an annual stipend of £21,805 for the 2026/7 academic year.

Requirements

The project involves three primary objectives: identifying and prioritising human NF1 variants, assessing their effects on NF1-dependent signalling, and validating the genetic variants in a zebrafish model. The student will use population data, AI-based biological foundation models, and human cell culture systems to screen variants, evaluate downstream signalling pathways, and test drug treatments such as MEK inhibitors targeting the Ras pathway. Furthermore, the student will establish a humanised zebrafish platform using CRISPR/Cas9-based genome editing to replace zebrafish nf1 sequences with human NF1 sequences, subsequently introducing selected variants via precise editing tools like prime editing and donor DNA-based knock-in to assess tissue patterning and pharmacological responses through transgenic reporter lines.