Up to 30% off — ends 2 Aug
ONLY00h00m00s
Up to 30% off — ends 2 Aug
ONLY00h00m00s
Medical Research Council (Cambridge)
4 months ago
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Cryo-EM and Mechanistic Analysis of Co-Transcriptional Splicing Medical Research Council (Cambridge) in United Kingdom
Degree Level
PhD
Field of study
Biochemistry
Funding
Full funding availableDeadline
Expired
Country
United Kingdom
University
Medical Research Council (Cambridge)
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About this position
This PhD project at the Medical Research Council (Cambridge) Laboratory of Molecular Biology investigates the fundamental mechanisms that coordinate transcription and pre-mRNA splicing in human cells. Accurate gene expression requires tight regulation between RNA polymerase II (Pol II) activity and the spliceosome, which removes introns from nascent RNAs co-transcriptionally. The laboratory has previously determined the structure of a transcribing Pol II-U1 snRNP complex using cryo-electron microscopy (cryo-EM), revealing direct physical interactions and providing mechanistic insights into early co-transcriptional splicing steps. Recent studies have shown that U1 snRNP is recruited to elongating Pol II via transcription elongation factors, and identified regulatory mechanisms that modulate transcription elongation rate, potentially coordinating transcription with RNA processing.
The PhD student will define the molecular interactions between transcription and splicing machineries, investigating how these facilitate efficient and accurate splicing. The project will focus on the structure and function of large co-transcriptional splicing supercomplexes and dissect the mechanisms that coordinate gene expression. Training will be provided in cryo-EM, mammalian cell biology (including CRISPR-Cas9 genome editing), in vitro reconstitution of large protein-RNA macromolecular complexes, and biochemical and biophysical assays. The student will join a collaborative research environment with access to state-of-the-art cryo-EM, biophysics, and mass spectrometry facilities.
Understanding the coordination between transcription and RNA splicing is fundamental to gene expression and has important implications for diseases such as cancer, where dysregulation of splicing is increasingly recognised. The project is suitable for candidates with a strong background in molecular biology, biochemistry, or structural biology. Experience with relevant techniques is desirable but not essential. Applicants should have a relevant undergraduate or master's degree and good communication skills.
Primary literature and reviews related to the project are provided, including recent publications in Science, Nature Structural & Molecular Biology, and Nature Communications. The application deadline is April 14, 2026. For further information and to apply, visit the project link.
Funding details
Full funding including tuition fees and living expenses is available for this position. The scholarship covers all educational costs and provides a monthly stipend.
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