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Huntington's disease (HD) is a devastating inherited neurodegenerative disorder which is caused by the expansion of the CAG repeat in the gene coding for the huntingtin (HTT) protein, making the protein more prone to misfolding. Expression of misfolded proteins frequently leads to the formation of intracellular aggregates, either in the cytoplasm or the nucleus. Aggregate formation is associated with oxidative stress in mitochondria and a breakdown in protein homeostasis, or proteostasis, through chaperone defects and impairment of the ubiquitin-proteasome system (UPS). Understanding the kinetics and thermodynamics of protein aggregation in the test tube and in a cellular context is our key goal.TEM image of amyloid fibrils formed from purified HTT exon 1 fusion protein.

Single fibril elongation assay provides insight into seeding mechanisms involved in Huntington’s disease (HD). We seek to understand the dynamic behaviour and the structure of the aggregates that can spread through the brain and contribute to the disease progression. By purifying and fluorescently labelling HTT exon 1 protein, we can monitor HTT aggregation dynamics by using multicolor super resolution microscopy techniques combined with transmission electron microscopy (TEM). We are using cellular HTT models, as well as mouse models in collaboration with Prof. Gillian Bates FRS at the UCL Huntington's Disease Centre.A cell expressing polyQ (red), an aggregsome deposits next to microtubule-organising centre (MTOC, green).

Super-resolution microscopy reveals aggregation dynamics in models of HD and AD.  We apply super-resolution microscopy, biochemistry, and mathematical model construction (in collaboration with Dr. Zaccone) to study the assembly and disassembly of single aggregate clusters in live cells, thereby providing mechanistic information on protein aggregation in cellular environment. Insights into the molecular mechanisms of autophagic degradation of aggregates will help us restore aggregate clearance.

Functional screening of bioactive peptides reveals inhibitors of reactive oxygen species. Amount of reactive oxidative species (ROS) in cells can be maintained by cellular antioxidants such as Glutathione GSH), Catalases, and superoxide dismutase (SOD). However, as we age and during disease ROS imbalance increases and therefore we require extra antioxidant compounds or molecules to assist the endogenous antioxidant machinery. We are conducting large scale functional screening to identify antioxidant small molecules or bioactive peptides (in collaboration with CIRCE) that may potentially have therapeutic value for oxidative stress related diseases.


Total Internal Reflection Imaging

direct Stochastic Optical Resolution Microscopy

Anti oxidant assays

Bioactive Peptides

Structured Illumination Microscopy

HTT and Amyloid beta cell lines