- Zaccolo Group Research Group
Postdoctoral Research Scientist
My research is focussed on cyclic nucleotide signalling in the heart. Cyclic nucleotides, such a cyclic AMP and cyclic GMP, are important second messengers that propagate hormonal signals from the extracellular space to targets deep within the cell. Their signalling activates concerted molecular events to increase the ability of heart muscle cells to contract. Cyclic nucleotide signalling is terminated by phosphodiesterases (PDEs), and this family of enzymes is therefore a potent target for heart failure treatments. However, at present PDE inhibitors only work well acutely. This is because of the broad effector spectrum of each of the PDE families.
My aim is to generate a comprehensive catalogue of interaction partners for distinct PDEs in heart muscle cells using proteomics, and to characterise these interactions towards designing more specific disruptors of PDE function. Additionally, I aim to functionally characterise specific PDE sub-complexes by identifying PDE-dependent phosphorylation sites using a combination of pharmacological inhibition and phospho-proteomics.
My fascination with cellular signalling led me to join the laboratory of Prof. Manuela Zaccolo as a BHF-funded postdoctoral scientist in August 2015, after finishing my PhD in Quantitative Cell Biology under the supervision of Prof. Jason Swedlow at the University of Dundee. My PhD research towards prevention of aneuploidy in human cancer cells was supported by a 4-year Cancer Research UK fellowship and focussed on endogenous phosphatase inhibition in dividing cells.
Cyclic AMP signalling in a heart muscle cell visualised with a FRET reporter
The same cell was imaged before (left) and after (right) stimulation of the cAMP pathway. When cytosolic cAMP concentrations rise after adrenergic stimulation of the cell, blue light emission of the FRET reporter increases and yellow light emission decreases. The colour of the cells in the image reflects a change in this ratio, as shown in the multi-coloured cAMP concentration gradient at the bottom.
The Ndc80 complex targets Bod1 to human mitotic kinetochores
Schleicher K. et al, (2017), Open Biology, 7
Bod1 regulates protein phosphatase 2A at mitotic kinetochores
Porter IM. et al, (2013), Nature Communications, 4
Synthetic lethal metabolic targeting of cellular senescence in cancer therapy
Dörr JR. et al, (2013), Nature, 501, 421 - 425