The effects of fluid flow on protein structure

Lead Research Organisation: University of Manchester
Department Name: Life Sciences

Abstract

A variety of physical and chemical perturbations are routinely used to probe protein structure. Mechanical perturbations have also been used and are particularly informative as they can allow the forces required to modify protein structure and function to be accurately quantified. We will explore and develop a new mechanical perturbation, fluid-flow turbulence, and assess its applicability for studying, and controlling, protein unfolding.Turbulent flows will be deliberately induced in purpose-built flow cells to cause unfolding in several test proteins and so identify suitable targets for further study. Protein unfolding will be characterised using Raman spectroscopy and Raman optical activity, as these are proven and informative techniques. The observed conformational changes will be correlated with the measure flow parameters to further refine flow cell design. From the new information obtained in this pioneering project we hope to assess the viability of this approach for future, and more focused, studies of controlling protein structure using flow characteristics.

Publications

10 25 50
 
Description This was a proof of principle funding project whose purpose was to establish new collaborations between young chemists and chemical engineers (the stated aim of EPSRC for this scheme). Therefore, we developed a new and successful collaboration that was able to subsequently secure major funding.
Exploitation Route The scientific outputs came from the following grant. The purpose of this grant, as stated by EPSRC, was to establish new collaborations, not produce new science. But our work relates to the aim of controlling aggregation of biopharmaceutical drugs, reducing sample loss (currently about 33% of drug sample is lost in production), increasing drug efficacy and bioavailability and reducing autoimmunogenic side-effects.
Sectors Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology

 
Description This pump priming grant established the collaboration between myself and Dr Balabani at KCL. As such the following grant (EP/F007922/1) was largely possible due to this first grant. As the original aim of the Chemistry/Chemical Engineering Interface Scheme was to establish long term funded collaborations this project was highly successful.
First Year Of Impact 2007
Sector Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology
Impact Types Societal,Economic

 
Description ALERT14
Amount £732,689 (GBP)
Funding ID BB/M011658/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 01/2015 
End 04/2015
 
Description Cross-Disciplinary Feasability Account
Amount £201,216 (GBP)
Funding ID EP/I016716/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 01/2011 
End 12/2011
 
Description King's College London 
Organisation King's College London
Country United Kingdom 
Sector Academic/University 
Start Year 2006
 
Description Melvin, Southampton CARS project 
Organisation University of Southampton
Country United Kingdom 
Sector Academic/University 
PI Contribution Conducted research, cpauthored paper and coapplicant on grant applications (unsuccessful)
Collaborator Contribution Condusted research, coauthored paper and coapplicants on grant applications (unsuccessful)
Impact Perney, N.M., Braddick, L., Jurna, M., Garbacik, E.T., Offerhaus, H.L., Serpell, L.C., Blanch, E.W., Holden-Dye, L., Brocklesbury, W.S. and Melvin, T., "Polyglutamine Aggregate Structure In Vitro and In Vivo; New Avenues for Coherent Anti-Stokes Raman Scattering Microscopy". PLOS One (2012), 7, e40536, DOI: 10.1371/journal.pone.0040536
Start Year 2011
 
Description Melvin, Southampton CARS project 
Organisation University of Sussex
Country United Kingdom 
Sector Academic/University 
PI Contribution Conducted research, cpauthored paper and coapplicant on grant applications (unsuccessful)
Collaborator Contribution Condusted research, coauthored paper and coapplicants on grant applications (unsuccessful)
Impact Perney, N.M., Braddick, L., Jurna, M., Garbacik, E.T., Offerhaus, H.L., Serpell, L.C., Blanch, E.W., Holden-Dye, L., Brocklesbury, W.S. and Melvin, T., "Polyglutamine Aggregate Structure In Vitro and In Vivo; New Avenues for Coherent Anti-Stokes Raman Scattering Microscopy". PLOS One (2012), 7, e40536, DOI: 10.1371/journal.pone.0040536
Start Year 2011
 
Description Melvin, Southampton CARS project 
Organisation University of Twente
Country Netherlands 
Sector Academic/University 
PI Contribution Conducted research, cpauthored paper and coapplicant on grant applications (unsuccessful)
Collaborator Contribution Condusted research, coauthored paper and coapplicants on grant applications (unsuccessful)
Impact Perney, N.M., Braddick, L., Jurna, M., Garbacik, E.T., Offerhaus, H.L., Serpell, L.C., Blanch, E.W., Holden-Dye, L., Brocklesbury, W.S. and Melvin, T., "Polyglutamine Aggregate Structure In Vitro and In Vivo; New Avenues for Coherent Anti-Stokes Raman Scattering Microscopy". PLOS One (2012), 7, e40536, DOI: 10.1371/journal.pone.0040536
Start Year 2011
 
Description The University of Manchester 
Organisation University of Manchester
Country United Kingdom 
Sector Academic/University 
Start Year 2006