Splicing factors help protect genomic fidelity

Stills from time-lapse movie of fruit fly embryos expressing GFP-tubulin (green) and RFP-Histone (red). Upper panel - control embryo. Lower panel -  embryo in which the splicing factor, Sf3A2, has been inhibited. Mitosis fails and chromosomes do not segregate correctly.

Inhibiting splicing factor Sf3A2 disrupts mitosis in fruit fly embryos. Read more.

Exploring mechanisms of cell-to-cell signalling

Cytonemes transport Wnt protein (red) between gastric cancer cells. A halo of Wnt protein can be observed around these cells and its diameter correlates with the average length of their cytonemes (green).

Cytonemes transport Wnt protein (red) between gastric cancer cells. Read more.

Cell and Molecular Biology and Development

Our research focus

Research in the Cell & Molecular Biology and Development theme aims at revealing fundamental molecular mechanisms to provide novel insights into cellular processes and functions, cell communication, the development of organisms, their interaction with pathogens, and the molecular basis and pathophysiology of diseases. Key research areas are the organisation of the cytoskeleton, organelle motility & motor proteins, organelle biogenesis & communication, cell polarity & shape, membrane trafficking & remodelling, mitosis & cell division, formation of cilia & flagella, genome organisation, DNA/RNA synthesis & gene expression, chromatin integrity & DNA damage response, generation of immune diversity, cell signalling processes, neuroscience & neuronal circuits, embryo development & environmental impacts, immune responses in plants, pathogen defences & fungal plant pathogenicity.

Our research combines different models including yeast, fungi, plants, marine worms, flies, fish and mammalian cells. We apply multi-disciplinary approaches including molecular cell biology, cell and developmental biology, proteomics, genetics/epigenetics, mathematical modelling & computational biology, systems biology, and biophysics.

Our research is supported by the Bioimaging Centre, the Exeter Sequencing Service, the Mass Spectrometry Facility and the Aquatic Resources Centre.

Recent research highlights

Splicing factors moonlight to protect genomic fidelity 

The more we learn about the complex networks of protein interactions cells require in order to grow and divide, the more "moonlighting" proteins are discovered. In a new multidisciplinary and collaborative study, James Wakefield and his group demonstrate conclusively that two proteins, Prp31 and Sf3A2, known for many years as core proteins involved in RNA splicing, have a separate role at the kinetochore during cell division. Their functions are conserved from flies to humans, suggesting they are just as important for mitosis as they are for splicing.

Pellacani C et al. (2018). Elife 7:e40325.

Unravelling the mechanisms of cell-to-cell signalling

The Wnt signalling proteins orchestrate development and tissue homeostasis in all multicellular organisms. Research led by Steffen Scholpp has now shown that signalling protrusions - called cytonemes - transport Wnt proteins between cells. The studies have investigated how cytonemes form using a combination of state-of-the-art genetic and high-resolution imaging techniques. This knowledge will help us to develop new ways to control Wnt signalling in embryogenesis and diseases.

Mattes B et al. (2018). Elife 7:e36953. | Read more here.

Visualizing the subcellular dynamics deep within living systems.

Visualization of cellular processes deep within tissues is an extreme challenge for modern microscopy. A research team including Steffen Scholpp, led by Nobel laureate and Janelia group leader Eric Betzig, has developed and validated a revolutionary imaging system that utilizes adaptive optics (the same technology used by astronomers) and lattice light sheet microscopy to provide high-resolution 3D movies of subcellular dynamics, including cancer cells crawling, spinal nerve circuits wiring up, and immune cells cruising through a zebrafish’s inner ear.

Liu TL et al. (2018). Science 360(6386). | View the movies here.

New insight into the localization of tail-anchored proteins

Tail-anchored (TA) proteins are targeted to organelle membranes, where they mediate critical cellular processes. While the correct targeting of TA protein to appropriate membranes is critical, the mechanisms and signals involved are not fully understood. A study led by Michael Schrader has provided unique insight into this process, identifying characteristic physicochemical features of TA proteins that allows prediction of their subcellular localization using a machine-learning approach.

Costello J et al. (2017). J. Cell Sci. 130(9):1675-1687. | Read more here.