Martin Walsh

We are a structural biology group based at Diamond light source which presents us with an arsenal of state-of-the-art techniques to determine the structures of macromolecules. We have used primarily X-ray crystallography in the past, but now combine this with biological small angle scattering (BIOSAXS) and cryo-electron microscopy. We complement our structural studies with a range of biochemical, biophysical and spectroscopic techniques to fully understand the function and the dynamics of the systems under study.
During the COVID19 pandemic our activities were fully diverted to applying a structure based drug discovery approach to the two cysteine proteases of SARS-CoV-2. We took a completely open-access approach to this work which led to the Covid Moonshoot initiative. A full summary along with experimental data can be found here. We continue to actively work on development of antivirals against coronavirus and emerging viral pathogens of concern through our participation in the ASAP Discovery Consortium which is a NIH Antiviral Drug Discovery (AViDD) U19 Center.

Bacterial pathogenesis

The main topic of research in the group is using a targeted structural and functional approach to understanding at the molecular level how bacteria cause disease. We have focused our efforts in the main part on respiratory bacterial pathogens that continue to pose a significant health risk to the very young and elderly and have identified a number of vital processes within these pathogens to characterize and assess as targets for drug discovery. Our interests lie predominately in understanding regulation of bacterial biofilms, the structural basis of bacterial adherence and antimicrobial resistance mechanisms.

After graduating from University College Galway (UCG) with a first class Honours degree in Chemistry in 1989, Walsh remained at UCG for his PhD work which used X-ray crystallography to fully characterize the flavoprotein, flavodoxin. This work aided in providing a general model for how flavoproteins modulate the redox potentials of flavin mononucleotide (FMN). The work was a significant milestone for structural biology in Ireland, as it presented the first protein crystal structures determined from an Irish-based research group.

Early postdoctoral work at York and EMBL Hamburg concentrated on the development and determination of protein structures at atomic resolution which was being pioneered at that time in Hamburg. This work contributed to introducing routine refinement of structures at this resolution as well as providing experimental data on the stereochemistry of amino acids in proteins.

In 1997 Walsh moved to Argonne National Laboratory (ANL) where he worked primarily on chaperonins and contributed to the commissioning of the world’s first dedicated insertion device beamline for exploiting anomalous diffraction in macromolecular crystallography: ID19 at the Advance Photon Source (APS). Work and associated research carried out at Argonne in the late 1990’s contributed strongly to establishing the MAD technique. In 1999 he moved to IRBM in Rome where work focused on the structural biology of the hepatitis C virus.

In 2001 he was appointed MRC group leader for BM14, based at the ESRF. Key hardware and software solutions to crystallography were delivered – automation of sample handling through robotics and management of crystallographic data (ISPyB) which have changed the way crystallographers now approach macromolecular structure determination at synchrotron beamlines.

In 2009, he joined Diamond Light Source with responsibility for life science research. 

He was made an Officer of the Most Excellent Order of the British Empire (OBE) for services to Science during Covid-19, in the King's first Birthday Honours List in June 2023.