Portrait of Dr Jose Luis Ortega Roldan

Dr Jose Luis Ortega Roldan

Lecturer in Biological NMR
Director, Master by Research Programme

About

Dr. Ortega-Roldan graduated in Chemistry at the University of Granada in 2005, where he conducted his PhD research in the laboratory of Prof. Nico van Nuland and Dr. Ana I. Azuaga-Fortes. During his PhD, Dr. Ortega-Roldan studied the structure, folding properties and interactions of the SH3 domains of the CD2 adaptor protein using NMR as the main technique and was awarded with an EMBO short-term fellowship to develop new NMR methodologies for the study of weak protein complexes in the laboratory of Dr. Martin Blackledge at the Institut the Biologie Structurale (Grenoble, France).
In 2011 he obtained a FEBS long-term fellowship to conduct his postdoctoral research in Dr. Jason Schnell laboratory at the University of Oxford studying membrane proteins by solution NMR. Subsequently in 2014 Dr. Ortega-Roldan was awarded a Marie Curie IEF fellowship to continue his research on the structure and function of the human Sigma-1 receptor.
Dr. Ortega-Roldan joined the School of Biosciences in September 2016 as a Lecturer in Biological NMR and head of the NMR facility, where his research group specialises in the structural and functional studies of proteins able to insert in lipid membranes, forming pores and channels.

ORCID ID: 0000-0002-6316-4390

Research interests

Integral membrane proteins and membrane-associated proteins are essential players in biological processes. Their functions range from transport across the membrane, cell adhesion and regulation of the cell shape. They represent around 40% of all proteins, and given their importance in the cell is not surprising that around 50% of the current drugs target membrane proteins. However, only a small number of structures of membrane proteins have been elucidated so far due to their low expression levels and the requirement of membrane mimetic environments for their study.
Our lab is interested in proteins with the ability to exists in a soluble form and in a membrane-bound form, where they usually form channels of pores. We study their mechanism of membrane insertion, the factors that trigger their activation and their inhibition using integrative structural biology tools, with a particular emphasis in solution NMR, as well as biophysics and fluorescence microscopy.
We are currently studying two protein families, the Chloride Intracellular Channel (CLIC) family, and MLKL:

  • Chloride ion channels control several cellular processes required for the normal function of the cell, and growing evidence supports the role of this channels in the development of different types of cancer. The Chloride Intracellular Channel (CLIC) has been linked with glioblastoma proliferative capacity and cardiac disease. We seek to identify which CLIC conformer is involved in disease and inhibitor binding, to understand the factors governing the equilibrium between the different CLIC forms and to determine the mechanism regulating such equilibrium with atomic detail. These information can be of great use for the development of conformation-specific pharmacological inhibitors and regulators that could lead to new avenues for cancer treatment. 
  •  Necroptosis is a process of controlled cell death that is part of the immune response to pathogens such as viruses. MLKL is a critical mediator of necroptosis that ruptures cellular membranes leading to cell death. Our work aims to elucidate how MLKL ruptures the membrane at molecular detail. This will enable the understanding and therapeutic manipulation/ exploitation of MLKL-mediated necroptosis for the treatment of viral infections.   

Teaching

Undergraduate:    

  • Biological Chemistry BI3212/BI3210/BI322/BI3220
  • BI514 Pharmacology
  • BI604 Biomembranes  

Postgraduate 

  • BI852 Advanced Analytical and Emerging Technologies for Biotechnology and Bioengineering 

Supervision

MSc-R projects available for 2020/21

In-cell structural biology: CLIC1 structure, function and drug binding inside tumour cells
CLIC1 is a chloride channel that gets upregulated in different tumour cells and whose inhibition has been shown to halt tumour progression. The aim of this project is to study the activation and inhibition mechanisms with atomic detail using a range of structural biology techniques, including NMR, X-Ray crystallography and fluorescence microscopy.
Additional Research costs: £1500
Understanding antimicrobial activity in live cells The mechanism of action of peptides and compounds with antimicrobial activity is not fully understood. We will combine in-cell NMR and in-vivo fluorescence imaging to understand how different peptides and organic molecules with antimicrobial activity kill bacteria. This information will enable the optimisation of these compounds for the next generation of antimicrobial agents.
Additional Research costs: £1500
Engineering proteins for the production of antimicrobial peptides Many protein and peptides can interact with the lipid membrane to form pores or channels. These have been found as toxins in nature and can be manipulated to be used as antimicrobial and anti fungal agents. However, there is a poor understanding about the membrane insertion mechanism and the protein sequence determinants. Our laboratory has recently developed new tools to study such interactions combining structural biology and cell biology techniques.
This project will combine molecular biology tools, biochemical assay and structural biology for the rational design of antimicrobials with optimised membrane insertion capabilities. The results will enable engineering new proteins and peptide with antimicrobial and anti-fungal activities.
Additional Research costs: £1500

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