Institute for Cell and Molecular Biosciences

Staff Profile

Dr Paula Salgado

Lecturer in Macromolecular Crystallography


Research Positions

2012 - present Lecturer of MacromolecularCrystallography, ICaMB, Newcastle University

2011 -2012 Research Associate, Division of Cell and Molecular Biology, Department of Life Sciences, Imperial College London, UK

2008 – 2011 Research Associate, Division of Molecular Biosciences, Department of Life Sciences, Imperial College London, UK

2005 – 2008 Research Associate, School of Crystallography, Birkbeck College/University College, London, UK


2001 – 2005 PhD in Structural Biology, Henry Wellcome Trust Building for Human Genetics, University of Oxford and Open University. "Structural Studies of RNA-dependent RNA polymerases"                         Supervisors: Dr Jon Grimes and Prof Dave I Stuart

1993 -1999 BSc in Biochemistry, Science Faculty & Institute of Biomedical Sciences “Abel Salazar”, University of Porto, Portugal. Research Project: "Structure determination of transthyretin variants"


Research Awards

November 2014 - November 2017 - New Investigator Research Grant, MRC

April 2013 - March 2014 - Royal Society Research Grant

March - June 2011 - Wellcome Trust Value In People Award

Oct 01 - Oct 2005 - PhD Fellowship (part of Human Frontier Science Program Research Grant)



As a Structural Biologist, my main research interest is in the determination and understanding of the structure of proteins associated to human disease.

I am particularly interested in proteins involved in disease caused by infectious agents, aiming at providing molecular details of key mechanisms of host-pathogen interactions, relevant for the development of more effective treatments.

Current focus in the lab is on proteins from two human pathogens particularly relevant in hospital environment: the bacteria Clostridium difficile and the fungus Candida albicans.


Clostridium difficile S-layer

C. difficile is now the most prevalent hospital acquired infection in the UK. These gram-positive bacteria have an outside para-crystalline layer (S-layer) that is presumed to act as a protective shield and that is thought to be implicated in virulence.

In collaboration with Prof Neil Fairweather at Imperial College London, we focus on understanding S-layer organisation, primarily by determining the structure of the major S-layer protein constituent, SlpA. We are also studying other cell wall proteins identified in C. difficile, aiming to understand their macromolecular details with our structural studies that complement work developed at Imperial College.


Fungal biofilms

Biofilms are microbial masses that adhere to biological or non-biological surfaces and have been implicated in both the spread and onset of infections. Importantly, they provide a protective environment as  microorganisms in biofilms are more resistant to antibiotics and host defences.

Candida albicans can cause a wide range of diseases and the formation of biofilms on catheters and medical implants is a significant source of systemic infections in the hospital environment.

The CFEM-containing family of proteins, characterised by an eight-cysteine motif unique to fungal species, has been implicated in biofilm formation and could provide a structural scaffold for new rational drug development.  Our research, in collaboration with Dr Carol Munro at the University of Aberdeen, is focusing on providing details into the structural organisation of this unusual motif and understand its role in candidal infections. 

Recently, while working at Imperial College London with Dr Ernesto Cota,  I determined the structure of the first candidal adhesin, Als9. The structural model allowed the identification of a flexible unusual binding cleft in these adhesins that accounted for the observed relatively unspecific ligand binding nature of the Als family. 


RNA-dependent RNA polymerases (RdRPs)

During my PhD, I determined structural models of several complexes of an RdRP of a dsRNA virus (bacteriophage Phi6) with template RNA and different cations, contributing to the elucidation of the mechanisms of initiation and inhibition of RNA polymerisation. This viral RdRP is a close structural homologue of the Hepatitis C virus polymerase and is therefore extensively used as a model enzyme. Structural information derived from the bacteriophage protein has allowed a better understanding of the replication mechanisms associated with the human pathogen, hence contributing to rational design and development of more effective treatments.

I also determined the structure of an RdRP involved in RNA silencing, the first such cellular polymerase model to be described. Surprisingly, the model revealed a catalytic site reminiscent of that found in the multi-complex enzymes involved in DNA transcription (DNA-dependent RNA polymerases, DdRPs). These observations prompted a structural-based evolutionary analysis of polymerases that highlighted unexpected links between RNA silencing and DNA transcription mechanisms.