Research focus
My research sits where chemistry meets the biology of neurodegeneration: how amyloid and tau proteins aggregate, how membranes shape that process, and how we can detect and counter it.
Interaction of amyloidogenic proteins with cell membranes
Amyloid-β (Aβ) can misfold into sticky aggregates that are toxic to neurons, and Aβ oligomers can insert into cell membranes and destabilise them. To understand how, I build simplified model membranes in the lab, sometimes adding specific membrane proteins, and follow Aβ binding in real time with fluorescence microscopy and electrical measurements.
This work is published in Biophysical Chemistry (2025), where we show how a membrane receptor modulates the assembly of Aβ aggregates, and how a drug can disassemble them, on asymmetric neuronal model membranes. Read the paper →
What we found
- Lipid composition matters. Membranes rich in negatively charged lipids such as phosphatidylserine are much more vulnerable to Aβ, even at low concentrations.
- A receptor changes the outcome. CD36, a fatty-acid receptor on brain immune cells, creates hotspots for Aβ nucleation. With it present, the same Aβ binding mixes lipid domains completely instead of only stiffening the membrane.
- Binding can be blocked. The plant compound ursolic acid was found to reduce Aβ binding and aggregation at membranes.
Synthetic chaperones to inhibit amyloid toxicity
Low-molecular-weight amyloid oligomers are among the most toxic forms of Aβ. I isolated the most toxic one, a tetramer, studied its biophysical properties, and then designed nanoparticles and polymers that bind amyloid and keep it from forming toxic assemblies, improving each design where the last one fell short.
Two further directions are under way: a small-molecule probe that binds Aβ and reduces oligomer-induced internal haemorrhage in mice (submitted), and a polymer chaperone that binds α-synuclein to stop its toxic aggregation (in progress). Read the paper →
What we found
- A nanoparticle can steer nucleation. A gold nanoparticle functionalised with N-methyl-D-aspartic acid regulates how amyloid tetramers nucleate and reduces their toxicity in vitro.
- A polymer can co-aggregate and disaggregate. A polyfluorene polymer carrying an isatin group blocks Aβ aggregation by forming non-toxic amyloid–polymer co-aggregates, and breaks up mature aggregates in human cerebrospinal fluid.
- It can reach the brain and protect neurons. Swapping isatin for benzimidazole gave nanodots that cross the blood–brain barrier and protect neurons in a wild-type mouse model, by binding the amyloidogenic region and blocking the oligomer-driven mitochondrial damage.
Other research directions
Liquid–liquid phase separation
How tau forms condensates, and how pH, temperature and crowding agents affect them.
Electrochemical device
A two-terminal device that detects low-molecular-weight amyloid oligomers in cerebrospinal fluid, for early Alzheimer's diagnosis.
Lipid nanoparticles
Nanocarriers for selective delivery of anti-cancer drugs, developed at Queen Mary University of London.
Techniques
I investigate complex biological systems with complementary reductionist models, using structural, optical, and electrochemical methods.
Imaging and structure
- Confocal laser scanning microscopy (Leica SP8 and Stellaris)
- Atomic force microscopy (air and liquid)
- Fluorescence lifetime imaging (FLIM)
Kinetics and dynamics
- Fluorescence correlation spectroscopy (FCS)
- Fluorescence recovery after photobleaching (FRAP)
- Protein aggregation assays (ThT)
Binding studies
- Isothermal titration calorimetry (ITC)
- Electrochemical impedance spectroscopy (EIS)
- MicroScale thermophoresis (MST)
- Fluorescence anisotropy
Model systems
- Tunable giant unilamellar vesicles (GUVs)
- Suspended lipid bilayer (symmetric and asymmetric)
- Porcine brain lipid extract