Does it work?
Dr Margarida Rodrigues (Faculty of Mathematics at Cambridge), first author of the paper, brought her biochemistry and biophysics background to help determine if the new molecule worked. “Developing a tool capable of isolating all small protein aggregates was exactly the type of exciting and challenging project that would take on,” said Dr Rodrigues. “I was particularly motivated by the ‘out-of-the-box’ design of CAP-1 as compared to the traditional use of antibodies where you can only study one type of protein at a time.”
The researchers spent several years using advanced microscopy methods to investigate how CAP-1 works. They found the new chemical antibody is highly selective to the beta-sheet structure of the protein oligomers, and also has potential advantages in terms of stability and resistance to degradation compared to conventional antibodies. This means that these previously difficult-to-detect protein oligomers can be comprehensively investigated for the first time. "It worked every time! It was so rewarding to ‘see’ CAP-1 capture the aggregates and recover them for further characterisation,” said Dr Rodrigues.
The final step in the process was to find out if the molecule worked in human samples. The group collaborated with Prof Henrik Zetterberg (UK DRI Group Leader at UCL), who has been studying biomarkers for Parkinson’s and Alzheimer’s diseases for over a decade and set up the UK DRI Biomarker Factory which launched earlier this year.
A key experiment was to show that when CAP-1 was used in human cerebrospinal fluid from healthy individuals or patients with Parkinson’s, it could also detect protein aggregates in the fluid, and even enrich them for further studies.
“We anticipate these new tools and methods will be used to detect and characterise the aggregates that initiate and drive the development of neurodegenerative disorders such as Parkinson’s disease,” said Prof Lee.
Read the Alzforum summary of this research.
To find out more about Prof David Klenerman, visit his UK DRI profile. To stay up to date on the latest research news and Institute updates, sign up to receive our monthly newsletter, ‘Inside Eye on UK DRI'.
Source: Yusuf Hamied Department of Chemistry, University of Cambridge
Reference: M. Rodrigues, P. Bhattacharjee, A. Brinkmalm, D.T. Do, C.M. Pearson, S. De, A. Ponjavic, J.A. Varela, K. Kulenkampff, I. Baudrexel, D. Emin, F.S. Ruggeri, J.E. Lee, A.R. Carr, T.P.J. Knowles, H. Zetterberg, T.N. Snaddon, S. Gandhi, S.F. Lee, D. Klenerman, Structure specific amyloid precipitation in biofluids, Nature Chemistry (2022).
Article published: 8 July 2022
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