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Pierre Rizkallah

Dr Pierre Rizkallah

Rcuk Fellow

School of Medicine

Email
RizkallahP@cardiff.ac.uk
Telephone
+44 652248
Campuses
Sir Geraint Evans Cardiovascular Research Building, Room 3/05, University Hospital of Wales, Heath Park, Cardiff, CF14 4XN
Comment
Media commentator
Users
Available for postgraduate supervision

Overview

I am a senior lecturer in Structural Biology. I specialise in studying shapes of biological molecules at the atomic level, to infer ways and mechanisms of interactions between different molecules of life. I have conducted research in many different fields of Life Sciences, affording an understanding of biological communications in a variety of systems. This opened up the ability to design therapies for different complaints, an area at the heart of my research. It is also an opportunity to design diagnostics and to use biotechnology to enable processes that do not occur naturally.

I am a Chemistry graduate, at BSc and PhD level. I use Physics applications to study biological macromolecules. I have extensive experience with X-ray crystallography and 3D structure determination using synchrotron radiation. I have used the allied techniques of Small Angle X-ray Scattering (SAXS) and Circular Dichroism (CD) to shed light on biological mechanisms.

I have served on committees and participated in programs at national and international levels. I have conducted many outreach and media exercises during the course of my career, communicating the immediacy relevance and importance of Science in everyday life.

I had a brief period of experience in the cosmetics industry, leading a production line team.

Publication

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Articles

Research

  • Adenovirus Modulation for Oncotherapy: We have subverted the natural adenovirus pathogen to be a delivery vehicle for cancer specific epitopes that can raise immunity against these cancers. The virus is first rendered non-proliferative by removing the replication exons, then a short stretch of coding nucleotides are inserted at a strategic point in the targetting protein on the sruface of the virus to mimic part of the cancer associated protein. When the target cells are infected, the epitope is expressed and the immune system is mobilised to recognise it, attacking all malignant cells. We have used structure determination extensively to gain information about the best strategy to employ in this effort, with around 20 new entries into the protein data bank. Collaboration with the group of Prof Alan Parker at the School of Medicine, Cardiff University.
  • Immune System Proteins: This work aims to determine the structural factors involved in the cross-reactivity of Thymus-derived cell receptors, TCRs, when they recognise more than one antigen presented in the context of the Major Histocompatibility complex, a mechanism underlying autoimmunity. A second aspect is the degeneracy of TCR binding to various antigens presented by one MHC to allow wide coverage of possible antigens with the limited number of MHCs an individual has. The project involves using X-ray crystallography for solving 3D structures of these entities, and conducting binding studies with surface plasmon resonance, isothermal titration calorimetry and naive T-cell activation. Colaboration with the T-cell Modulation Group led by Prof Andrew Sewell, in the Institute of Infection and Immunology, Cardiff University.
  • Enhanced Green Fuorescent Proteins: The green fluorescent protein from Aequoris victoria is currently used in many biological and biotechnological applications to aid in mapping the distribution of biological entities in cells, via attaching it to antibodies raised against molecules of interest. Upon binding, the GFP carrying antibody fluoresces at specific wavelengths. A program of genetic engineering of the GFP from the jelly fish Aequoria victoria aims to enhance its fluorescence properties for better visibility. Collaboration with Dr Dafydd Jones in the School of Biosciences at Cardiff University.
  • Natural Bacterial Insecticidal Toxins: We are studying various natural toxins produced by Bacillus thuringiensis and similar organisms to understand their mode of action and to develop environmentally friendly pesticides that can be targetted at specific pests. Collaboration with Prof Colin Berry in the School of Bioscineces at Cardiff University.
  • Calpain Inhibitor Design: Calpain is a multi-domain caspase involved in response to inflammation. It helps white blood cells change shape to cross through epithelial tissue near inflammation sites. Too much activity is associated with arthrhitis after heightened response level. Inhibition of Domain VI had been achieved in the past, elsewhere, working with the porcine enzyme. Here, we are working on the human enzyme, trying to optimise the inhibitor for higher affinity and improved recognition. Collaboration with a team led by Prof Ruedi Allemann in the School of Chemistry, Cardiff University.
  • Biocoloration in lobster shell: The structure of β-crystacyanin, the coloured protein in lobster shell, was solved using softer X-rays to phase diffraction data. The structure delineated the mechanism by which light is abosrbed and modulated by the protein to effect a different emission in the visible spectrum by influencing the conformation of the astaxanthin chromophore bound by the protein. New methodology was developed to use the anomalous signal from S atoms in order to solve the structure. Collaboration with Prof John Helliwell, Manchester Unversity.
  • Carbohydrate Recognition: Binding of carbohydrate substrates by various lectins was studied in this project. The mode of binding of oligomaric mannose branches by monocot lectins and sucrose binding by legime lectins were studied. Collaboration with Prof Colin Reynolds, Liverpool John Moores University.
  • Snake Venom Proteins: The a-neurotoxin of the kign cobra Naja kaouthia and the haemorragin of Bothrops jararaca were studied in collaboration with Prof RDG Theakston, Liverpool School of Tropical Medicine.

Teaching

  • Introduction to Structural Biology module in Bioinformatics MSc course
  • Structural Biology for Medical undergraduates, as student selected component
  • Mentoring undergraduate Medical students

Biography

Education

  • 1984: PhD Chemistry, Nottingham University, UK
  • 1979: BSc Chemistry, Lebanese University, Beirut, Lebanon

Career Overview

  • Senior Lecturer / RCUK Senior Fellow, Cardiff University, since Dec 2008
  • Protein Crystallography Facility Manager, Synchrotron Radiation Source, Daresbury, UK. 19 Feb 1990 - 30 Sep 2008
  • Higher Scientific Officer, Agriculture and Food Research Council, Reading, UK. 2 Jan - 15 Feb 1990
  • Senior Research Fellow, Liverpool University and Daresbury Laboratory, UK. 1 Nov 1987- 31 Dec 1989
  • Post Doctoral Research Assistant, Leeds University, UK. 1 Dec 1984 - 30 Sep 1987
  • Production Line Manager, International Cosmetics Manufacturers S.A.L., Beirut, Lebanon. 1 Sep 1979 - 31 Aug 1980

Committees

  • Treasurer, Biologicsl Structures Group of the British Crystallographic Association, 2008-2017
  • Scientific Advisers Committee, SESAME Synchrotron project, Middle East, 2000-2004
  • Synchrotron Radiation Users Forum, 1997-2007
  • Secretary to the Beamtime Allocation Panel, SRS Daresbury, 1990-1995

Supervisions

New funding as co-supervisor for a student, starting in October 2021, to study adenoviruses.

Engagement

Cardiff University Structural Biology Network

Coordinating meetings to discuss matters related to the topic of Structural Biology. Presentations by visiting scientists or members of Cardiff University.

Cardiff University Beamtime Allocation Group at Diamond

Coordinating access to the facilities at the Diamond Light Source National Facility at Harwell, for X-ray crystallography, Small Angle X-ray Scattering, Circular Dichroism spectroscopy, Biological Imaging, etc.