Highlights of our research
Structural Biology in the department rests on the strong foundations laid by JD Bernal, who pioneered the application of X-ray crystallography to determine protein structure and who set up a Biomolecular Research Laboratory at Birkbeck in 1948.
Since then, progress in understanding biological systems has increased enormously, because multicomponent complexes that are tens of nanometers in dimension can be visualised as a result of technological developments in crystallography, image particle reconstruction using electron microscopy and solution spectroscopy.
How we are driving these innovations...
- The Orlova and Topf laboratories are developing mathematical methods .
- The Wallace laboratory is developing the application of synchrotron radiation circular dichroism spectroscopy for characterisation of macromolecular interactions.
- Developments in nuclear magnetic resonance spectroscopy pursued by the Christodoulou laboratory are enabling the folding of polypeptide chains to be analysed inside cells whilst still attached to the ribosome.
Looking at detailed images of large protein structures, for example, leads to ideas on how these nanomachines work, how they go wrong in disease and how they are exploited by pathogens.
Recent research highlights...
- A recent research highlight in the areas of structural biology and microbiology that required expertise in molecular biology, cryo-electron microscopy and X-ray crystallography features the imaging of a secretion nanomachine spanning the inner and outer membranes of Gram-negative bacteria. This work from the laboratory of Gabriel Waksman was published in Science and Nature during the course of 2009.
- The structures are of great significance to public health, as they suggest mechanisms that underpin the transfer of antibiotic resistance.
- The Saibil laboratory has now set up cryo-electron tomography, which will help to bridge the resolution gap between nanometer and micrometer-scales.
Cell biology covers many scales of spatial and time dimensions and includes studies of all the subcellular organelles and their interactions with cytoplasmic networks, systems and processes that produce a living cell.
Our discoveries include...
- Carolyn Moores has published in Journal of Molecular Biology a view of the interaction between a motor protein and a microtubule, key components of the cytoskeletal system that control cell division.
- Information gained from Structural Biology can be placed within a cellular context when protein components of macromolecular complexes are labelled with fluorescent dyes and then imaged within cells using light microscopy: Richard Hayward has published in Cellular Microbiology how exploitation of host cell biology by pathogens reveals information on the regulation of the cell cytoskeleton by kinases, a class of enzymes that regulates most cellular processes.
- Andrew Osborne has published in details of how malaria parasite in blood cells can export proteins across its endoplasmic reticulum.
A focus of the department is to understand how protein molecules and machines with complicated 3D structures are subject to quality control checks by a class of proteins known as chaperones. Some proteins require a chaperone in the early stages of their lifecycle, or whenever they show signs of unfolding, or not working properly.
What we have discovered...
- The Saibil Lab has published in Nature images of one cellular machine in the act of encapsulating a newly folded protein within the chaperone chamber. This kind of process is required to prevent proteins from aggregation, which would lead to protein deposition diseases.
- The Saibil Lab has published in Molecular Cell how a different protein re-modelling machine deals with proteins after they have aggregated. These machines and the cellular processes in which they participate are of great interest in the fight to prevent many degenerative diseases that stem from protein aggregation.
- Cara Vaughan in Molecular Cell has provided insights into how kinases can be regulated by their complex formation with the stress chaperone protein Hsp90.
- The 3D structure of a core component of a stress protein that protects a range of vulnerable proteins in the human neuromuscular system has been published in Journal of Molecular Biology (laboratories of Keep and Slingsby).
- Progress in combining technologies to unravel the quality control role of a flexible tumour suppressor protein complex, described as the Guardian of the Genome, has been reviewed by Elena Orlova in Current Opinion in Structural Biology.
The function of a folded protein often stems from pockets inside the protein that bind metabolites. Knowledge of 3D structures of proteins linked to pathology sets the stage for chemical biology and computational biology to play a role in drug discovery by designing small molecules that fit into these pockets.
Some of our findings...
- A paper published in Journal Molecular Biology has contributions from three group leaders (Gooptu, Nobeli, Barrett), who have combined their expertise in Structural Biology, Computational Biology and Chemical Biology to work out mechanisms of a specific protein-folding disease that causes emphysema.
- A study by Katherine Thompson has recently been published in Atmospheric Environment on the topic of the impact of oxidants in the air on lipids in the fluid lining human lung.
The balance of forces between interacting macromolecules in their aqueous environment, which drives the assembly of functional biological nanomachines, is studied by Biophysics.
Examples of recent research...
- A study of artificial self-assembled nanoparticles from the laboratory of Salvador Tomas was published in Journal of the American Chemical Society.
- Neil McDonald, using X-ray crystallography and calorimetry, has published in EMBO Reports how kinase enzymes, which are hot drug targets for the pharmaceutical industry, can be regulated by adaptor proteins.
- Mark Williams has published in the thermodynamic characterisation of protein-ligand/inhibitor interactions in the context of rational drug design.
- Konstantinos Thalassinos in is using new technological developments in mass spectrometry to monitor the shape change associated with the conversion of normal prion protein to the scrapie form.
- Studies reported in Biochimica et Biophysica Acta by the Wallace laboratory show how the dynamic sodium channel, a membrane protein of great interest in biomedicine, has great conformational stability.
- Professor Wallace’s contribution to the development of circular dichroism spectroscopy as a biophysical tool to study protein interactions was recognized by her being awarded the 2009 Interdisciplinary Prize of the Royal Society of Chemistry and the 2010 AstraZeneca Award.
Developments in genome sequencing and downstream array technologies and the ever-increasing size of the ProteinDataBank has driven Computational Biology to find ways of extracting information from deposited data, and developing the modelling of systems behaviour across fields of study.
Find out more...
- Irilenia Nobeli has reviewed in Nature Biotechnology the issue of promiscuity in protein interactions and its impact on drug discovery.
- Adrian Shepherd has published in Bioinformatics how modelling antigenic shift in influenza A H3N2 can give better predictive performance which will help to predict the efficiency of vaccines, whilst David Moss in Molecular Immunology has shown computationally that vaccine antigens are lacking in peptide sequences that bind T cells.
- Alona Sosinsky has published in Nature how the DNA sequence encodes shape in the double helix that can be exploited for gene regulation.
Above all of these scales of investigation, is Microbiology and Organismal Biology, which includes the traditional subjects of Botany and Zoology and includes the new field of translational medicine.
- Microbiological insights has led Sanjib Bhakta and Nick Keep to characterise in 3D a potential therapeutic enzyme target against a global human mycobacterial pathogen, published in Tuberculosis.
- Bibek Gooptu, in Annual Reviews of Biochemistry has surveyed the protein folding disorders known as the serpinopathies and considered how treatments can be developed to block liver cirrhosis, dementia and emphysema.
- Martin Ingrouille has shown how molecular systematics can address issues in Liliaceae taxonomy in a review in Annals of Botany.
- Cecil Terence Ingold, a leading mycologist of the twentieth century and former Chair of Botany in Birkbeck, died this year aged 104. He applied biophysical studies to the dispersal of fungal spores.
- Jane Nicklin’s (Faull) investigation into the role of fungal infections to control greenhouse pests published in Biocontrol has ensured that research into environmental mycology continues at Birkbeck.