Andrew Hudson

Biospectroscopy and imaging

Andrew Hudson 2.0

Research Summary

My research group’s aim is to bring frontier technologies in spectroscopy, imaging, photonics and microfluidics to bear on problems at the life-science interface.

A particular area of interest is the application of specialised techniques in fluorescence imaging to monitor the dynamics of single molecules. Differences in chemical reactivity might arise from small variations in the conformational structure of proteins and nucleic acids, however, the dynamics of individual molecules are not revealed in traditional experiments. Instead, the results reflect the ensemble average across the entire population of molecules. It is the objective of single-molecule research to reveal sub-population heterogeneity. With Professor Ian Eperon, we are applying single molecule methods to address otherwise inaccessible problems in RNA splicing. These have included validation of the spice-site selection model and the pathways for the early stages of spliceosome assembly and 3′ splice-site selection. We have also invented a technique to encapsulate single biological molecules in aqueous microdroplets within a water-in-oil emulsion. The approach enables single molecule fluorescence measurements to be made on freely-diffusing molecules, and eliminates the normal requirement to tether molecules to a solid support (the technology has been patented by the University).

On a different theme within the research group, we apply a number of imaging modalities to quantifying the distribution of hemoproteins in living cells, and how this distribution evolves in response to different stimulants. We are able to distinguish between the identity of the proteins, and the oxidation and coordination state of the metal. Recently, using Raman imaging, we have been able to provide mechanistic evidence for how small molecules (NO, CO) might confer protection on cardiomyocytes (heart cells) via their interactions with hemoproteins. We are also working with Professor Emma Raven to develop optical sensor technology for in vivo quantification of labile heme.

A number of years ago, whilst working on lab-based atmospheric measurements, the group invented a technique to monitor the binary coalescence of liquid-aerosol microdroplets using holographic optical tweezing combined with elastic and inelastic scattering measurements. The method was able to report on the binary coalescence time, and surface tension & viscosity of the composite microdroplet. We now employ the same technique to reveal chemical and physical changes in cells and synthetic lipid vesicles. With Professor Russell Wallis, we are looking at the real-time process of pore formation by the toxin, pneumolysin, in liposomal membranes, and with Dr Natalie Garton (Infection, Immunity and Inflammation), we are looking at how an aerosolised bacterium responds to osmostic stress.

Digital-droplet microfluidics is being used for both single-cell and single-molecule analysis
Digital-droplet microfluidics is being used for both single-cell and single-molecule analysis

Stepwise photobleaching (and blinking) of molecular fluorophores reveal the stoichiometry ofbiological complexes
Stepwise photobleaching (and blinking) of molecular fluorophores reveal the stoichiometry of biological complexes

Using a combination of microfluidics, optical tweezing and spectroscopy, we can study the effects of osmotic stress on a single bacterium or protein adsorption on the membrane of a lipid vesicle
Using a combination of microfluidics, optical tweezing and spectroscopy, we can study the effects of
osmotic stress on a single bacterium or protein adsorption on the membrane of a lipid vesicle

Key Publications

Group Members:

Simon Fung, Liam Collard, Faizal Patel, Galvin Leung, Leanne Blount, Beth Stone (joint with Ian Eperon)

To see Andrew Hudson's departmental home page, please click here.

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