Beth Bromley's Research Page

Current work

My research centres on the elucidation and exploitation of biologically relevant self assembly mechanisms. Current projects include:

Designed Protein Nanostructures

As part of an international collaboration between the labs of Paul Curmi, Heiner Linke, Nancy Forde and Dek Woolfson aimed at generating a designed protein motor, we have been generating coiled coil based nanostructures to act as self-assembling hubs. This work has raised new questions concerning our understanding of the specificity and oligomerization state energy landscapes and taught us about the design of flexible linking regions required to isolate coiled coil domains.

Design for a protein motor that walks along DNA

Design for a protein motor that walks along DNA

Some designs for coiled-coil nanostructures

Some designs for coiled-coil nanostructures

Peptide switches

I am working on rational design and characterisation of peptide sequences which adopt different structures and oligomerisation states based on the application of an external switch.

Merge sequence for a designed switch between a trimeric coiled coil and a zinc-finger structure

Merge sequence for a designed switch between a trimeric coiled coil (blue) and a zinc-finger structure (red)

The goal of this project is to explore the possibilities of hybrid sequences which contain the information for two separate structures and to develop an algorithm for producing switches based on a range of external triggers. Previous work in this area has focused on the ZICO systems which form oligomeric coiled coils with no metal ions present, but which switch to a monomeric zinc finger conformation upon the addition of zinc. However, in order to add a switching component to the motor design discussed above, the design of a minimal atpase is of primary interest.

Another goal for the design of peptides that have more than one native fold is to explore the physics behind the energy landscape of switching systems. This project will use short sequences so that modelling of the complete energy landscape is possible and the ability of such sequences to produce materials that convert chemical potential into mechanical work will be explored.

Coiled-coil specificity

We are interested in the rules which allow a protein composed of multiple coiled coils to fold into the correct conformation. We wish to know which motifs code for the various oligomeric states as well as anti-parallel versus parallel in order to create a library of mutually exclusively partnering peptides which can be combined to assemble to specific and novel geometries.

Previous work

In my final year undergraduate project I measured the properties of starch under flow using confocal microscopy. I wrote a computer algorithm to find and track particles and correlate there positions and motion.

During my Ph.D. I worked to characterise and model the self assembly of B-lactoglobulin which assembles both non-specifically near its iso-electric point and specifically to form an amyloid motif at both high and low pH. Both of these forms of self assemble appear to be generic to globular proteins.

Also within my Ph.D. I characterised the higher order assembly of fibres whether to create spherulites. These spherulites can be useful in characterising the assembly as well as dye binding properties due to their liquid crystalline nematic like order.

I have also worked on the exchange properties of wild type and amyloidogenic human transthyretin. This protein exists as a tetramer which undergoes subunit exchange which may be a key process in the production of amyloid deposits.

Recent publications

[1] "The Tumbleweed: towards a synthetic protein motor" Bromley, E. H. C., Kuwada, N. J. et al. HFSP J. 3 pp204-212, 2009

[2] "Designed alpha-Helical Tectons for Constructing Multicomponent Synthetic Biological Systems" Bromley, E. H. C., Sessions, R. B., Thomson, A. R. Woolfson, D. N. J. Am. Chem. Soc. 131 pp928, 2009

[3] "Peptide and protein building blocks for synthetic biology: From programming biomolecules to self-organized biomolecular systems." Bromley, E. H. C., Channon, K. J., Moutevelis, E. Woolfson, D. N. ACS Chem. Biol. 3: pp38-50, 2008.

[4] "Confocal microscopy of a dense particle system." Bromley, E. H. C. and Hopkinson, I. J. Colloid Interface Sci. 245: pp75-80, 2002.

[5] "Aggregation Across the Length-scales in beta-lactoglobulin." Bromley E. H. C., Krebs M. R. H. and Donald A. M., Faraday Discuss., 2005, 128.

[6] "The Binding of Thioflavin-T to Amyloid Fibrils: Localisation and Implications." Bromley E. H.*, Krebs, M. R. H., and Donald, A. M., J. Struct. Biol. 2005, 149(1): 30-7.

[7] "The Mechanism of Amyloid Spherulite Formation by Bovine Insulin." Krebs, M. R. H., Bromley, E. H. C., Rogers, S. and Donald A. M., Biophys J 2005, 88(3):2013-21.

[8] "Optical microscopy of growing insulin amyloid spherulites on surfaces in vitro." Biophysical J. 2006 90 (3):1043-1054

[9] "L55P transthyretin accelerates subunit exchange and leads to rapid formation of hybrid tetramers." Bromley E. H. C.*, Keetch, C. A, McCammon, M. G. Christodoulou, J. and Robinson C. V. J.B.C. 2005, 280 (50):41667-41674.

[10] "Mechanisms of Structure Formation in beta-lactoglobulin Heated Near the Isoelectric Point." Bromley E. H. C. and Donald A. M. Submitted to EPJ:E

(*Joint first author)