Allen group website

Page
Menu
News
Home > Research > Completed projects (for now) > Protein self-assembly

Protein self-assembly

The assembly of protein molecules into larger structures, such as filaments, is implicated in a number of  diseases, as well as presenting an opportunity for making new materials that might be useful in biotechnology. Since 2007, I have collaborated with my colleague Cait MacPhee on a joint experimental-theoretical programme of research to understand better the kinetics of how proteins form a particular class of filamentous structures, called amyloid fibrils. These are found in the brains of people with neurodegenerative diseases such as Alzheimer's, although it is not yet know whether it is the fibrils that actually cause disease or rather the small protein aggregates that form prior to the assembly of large fibrils. Cait and I have worked together with a number of students and postdocs to try to make a link between the types of measurements that we can do in our lab: i.e. the dynamics over which fibrils are observed when we apply denaturing conditions like a change of temperature, and the molecular mechanisms leading to fibril formation. 

 

In particular, two of our students, Ryan Morris (experiments) and Kym Eden (simulations) worked together to study the kinetics of fibril formation by the protein bovine insulin. From unexpected signatures in the kinetics of this process, they discovered that it is likely that insulin fibrils form "bundles" as they are created, which may have important implications for the likelihood of observing potentially toxic small aggregates in disease. 

 

More generically, Kym has also investigated using simulations the earliest step in the firbil formation process: the formation of a fibril nucleus. His work showed that this process is likely to be more complex that is currently appreciated: current models cannot explain characteristic "kinks" that are found in lag time-concentration curves. 

 

We have also investigated the kinetics of fibril formation by the "egg white" protein ovalbumin. Interestingly, this protein forms ring-like fibrils which show very different kinetics from, for example, insulin. 

          Recently, together with our postdoc Juraj Szavits-Nossan and our colleague Martin Evans, we have also started to investigate the question of stochastic 

variability in the kinetics of autocatalytic protein self-assembly. It is well-known that different patients with neurodegenerative diseases will develop symptoms at different times, but the processes that lead to this variability are unknown. We developed theroetical formulae that predict the amount of variability in amyloid fibril formation kinetics, and compared our predictions to existing experimental data. This study should provide a starting point for understanding better why variability arises in these self-assembly processes in nature.

 


 

    R. Morris*, K. Eden*, R. Yarwood, L. Jourdain, R. J. Allen and C. E. MacPhee 

Nature Communications 4, 1891 (2013) (* = equal contribution)


« prev top next »
Page
Menu
News
25/08/2022

Here is a great 3 minute video of our PhD student Freya Bull describing her research modelling bacterial infection of a urinary catheter!

25/08/2022

We are searching for a part-time computer systems administrator for our group in Jena. Please contact us if you are interested!

18/08/2022

Welcome to Ariane Zander who has joined us as a technician in our lab!

 
 

 

 
 
 
 
 
Page
Menu
News

Powered by CMSimple | Template: ge-webdesign.de | Login