Research Groups > Clair Baldock
Tel: +44 (0)161 275 5349
Recent key publications
Baldock, C., Oberhauser, A.F., Ma, L., Lammie, D., Siegler, V., Mithieux, S.M., Tu, Y., Yuen Ho Chow, J., Suleman, F., Malfois, M., Rogers, S., Guo, L., Irving, T.C., Wess, T.J., & Weiss, A.S. (2011). Shape of tropoelastin, the highly-extensible protein that controls human tissue elasticity. PNAS USA. 108:4322-7.. PubMed link
Tooley, L. D., Zamurs, L. K., Beecher, N., Baker, N. L., Peat, R. A., Adams, N. E., Bateman, J. F., North, K. N., Baldock, C., and Lamande, S. R. (2010) Collagen VI microfibril formation is abolished by an 2(VI) von Willebrand factor A-domain mutation in a patient with Ullrich congenital muscular dystrophy. J Biol Chem. 285:33567-76. PubMed link.
Berry, R., Jowitt, T. A., Ferrand, J., Roessle, M., Grossmann, J. G., Canty-Laird, E. G., Kammerer, R. A., Kadler, K. E., and Baldock, C. (2009) Role of dimerization and substrate exclusion in the regulation of bone morphogenetic protein-1 and mammalian tolloid, Proc Natl Acad Sci U S A. 106, 8561-6 PubMed link.
CLAIR BALDOCK BSc, PhD
Matrix protein structure
The research in my laboratory focuses on the hierarchical assembly and structure of extracellular matrix proteins. Many molecules of the extracellular matrix undergo complicated polymerisation to form fibrillar assemblies. The analysis of the structure and function of these assemblies is often complicated by their complexity. However, the novel application of structural biology and biophysical techniques is beginning to reveal exciting insights into their molecular assembly and structural organisation.
We are using a range of techniques including small angle X-ray scattering (SAXS), cryo-TEM with single particle analysis and electron tomography to tease out the structural details. Our main research focus is on the structure of two classes of microfibrillar proteins.
Firstly we are analysing the structure of fibrillin-1, an elastic fibre protein that has a principal role in the structure and function of organs that require elasticity, such as large arteries, lung and skin.We are using a combination of complimentary techniques to interrogate the molecule structure using SAXS and single particle image analysis. Via these methods, a very compact region of the molecule has been identified that was previously thought to be rigid and rod-like, significantly this region contains the binding motifs for integrins and heparan sulphate. At the next level of hierarchy,we are analysing whole microfibrillar assemblies, using cryo-TEM and treating the repetitive microfibrillar structure as a string of single particles.With these new methods we have identified individual molecules within the microfibril repeat and have described their organisation in a concertina fashion which reveals a mode of extension.
Secondly, we are analysing the structure of collagen VI microfibrils. Collagen VI has a ubiquitous distribution throughout connective tissues but is particularly enriched close to cells and around basement membranes where it forms a molecular bridge between cells and other matrix components. Mutations in the collagen VI genes give rise to heritable muscular dystrophies, highlighting its vital role in muscle anchorage. The goal of this research is to define the molecular organisation of collagen VI microfibrils, to understand its biological roles and to define the abnormal structures found in pathological tissues.