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The University of Southampton
Biological Sciences
Phone:
(023) 8059 4415
Email:
Ivo.Tews@soton.ac.uk

Dr Ivo Tews PhD, PD

Lecturer in Structural Biology, Admissions Tutor - Natural Sciences, Principal Investigator (Protein-Protein and Protein-Ligand Interactions)

Dr Ivo Tews's photo

Dr Ivo Tews is Lecturer in Structural Biology within Biological Sciences at the University of Southampton.

Career History

2010-present: Lecturer in Structural Biology. University of Southampton, UK.
2004-2010: Research Assistant (C1). Heidelberg University, Germany.
2000-2004: Postdoctoral Research Fellow. Heidelberg University, Germany.
1996-2000: Postdoctoral Research Fellow. NIMR Mill Hill, London, UK.

Academic Qualifications

2004-2011: PD (habilitation) venia legendi in Biochemistry and Biophysics
1992-1996: PhD in Crystallography. Heidelberg University, The EMBL outstation, Hamburg, Germany.
1985-1991: Diploma in Biological Sciences. Heidelberg University, Germany.

Research interests

Vitamin B6 Biosynthesis

Vitamins are low molecular weight compounds that have to be taken up into our cells in trace amounts, and vitamin deprivation leads to disease. In the body, vitamins often serve as enzymatic cofactors. Studies of their biosynthesis by human pathogens are of particular interest in order to develop specific drugs. 

We study the enzyme complex PLP synthase that is capable of synthesising the vitamin B6 (pyridoxal 5-phosphate, PLP) from two simple carbohydrate precursors and ammonium salts. With our unique approach of combining crystallography and spectroscopic techniques, we characterised the biosynthetic activity in protein crystals, and delivered structural snapshots of several stable reaction intermediates. The work led to the discovery of an entire novel use of imine chemistry in enzymes. 

Better understanding of the precise biochemical mechanism of this enzyme is key to developing novel inhibitors. We are advancing the understanding using nano-crystallographic techniques and X-ray Free Electron Laser science (XFEL) to resolve catalytic steps.

Read more:

Significant discovery of vitamin B6 biosynthesis enzyme

The remarkable complexity of vitamin B6 biosynthesis

Pdx

Pdx1-I320

I320 is a covalent reaction intermediate in vitamin B6 biosynthesis

Pdx1-I320

David Blow Prize success for Dr Ivo Tews

Cyclic Nucleotides in Bacterial Biofilms

Bacterial biofilms are sessile microbial communities recognised for compromising health. Biofilm formation is a bacterial persistence mechanism that can lead to chronic infection in human patients, with associated morbidity and mortality. Bacteria in biofilms are a major health problem as they are highly tolerant against antibiotic treatment. 

Our research aims to understand the mechanisms that promote bacteria to disperse from the biofilm state, reducing chronic infection and lowering antibiotic tolerance. A central regulator in this process is the bacterial signalling molecule cyclic di-guanosine-mono-phosphate, c-di-GMP. Our research is focussed on the control of the c-di-GMP balance, and we have determined the first structure of a dual active enzyme MorA that can both synthesise and break-down c-di-GMP. We are studying the activation of phospho-diesterase enzymes that are central in biofilm dispersal.

Understanding how c-di-GMP levels impact on biofilm development provides a novel opportunity to target bacterial resistance to antibiotics. Our efforts integrate with the efforts of the National Biofilms Innovation Centre

Read more

Bacterial Warfare The scientists tackling antibiotic resistance

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FebsLett

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Bacterial nutrient acquisition

To understand bacterial adaptation, we study bacterial enzymes and ABC transporters. The multi-disciplinary approach brings together structural biology, cell biology and marine microbiology (National Oceanography Center).

To understand how bacteria thrive under extreme conditions of nutrient depletion we study iron binding proteins that are important for iron uptake and can also perform intracellular functions. Structural insight derives a novel model of iron homeostasis in Trichodesmium, a cyanobacterium accounting for approximately half of the total marine nitrogen fixation worldwide. 

Our work is of fundamental importance to better understand how bacterial adaptation strategies can be exploited for biotechnology and future biofuel technologies, and how they might impact on survival mechanisms in human pathogens. 

Methods development

The discipline of macromolecular crystallography is at an exciting juncture that is dependent on the development of insightful experiments that are driven by a fast-evolving technology.

As a partner in Diamond’s VMX project we will reduce demands on sample amount by development of nano-crystallography. Together with advances in data collection and analysis we are already adding time resolution to the crystallography, to provide better insight into molecular mechanisms, and to better represent and understand biological systems. 

We develop methods in multi-crystal serial crystallography and study the effects of radiation-induced damage in biological samples. To improve crystallographic data collection and data analysis, we are closely linked up with CCP4, a computing suite that has revolutionised the speed and ease of applying X-ray crystallography to solve healthcare, biological and medical problems.  

Read more

Southampton research team invited as first users to new state-of-the-art facility

First users on VMXm

CCP4 Collaborative Computational Project No. 4 Software for Macromolecular X-Ray Crystallography

Immunology Research

Structural biology provides fundamental mechanistic insight that underpins and greatly enhances collaborative research. 

We have generated a better understanding of lipid antigen presentation, a process that in the human immune system is not well understood. Our structures of protein-lipid complexes provide an essential basis for computational chemistry and the discovery of cholesterol-esters as an entirely novel class of immune ligands (with Dr Mansour, Prof Elliot, Medicine and Prof Essex, Chemistry). This has led to a paradigm shift in the field of antigen presentation.

The field of antibody therapy is not only today’s favourite recipe for creating blockbuster drugs in autoimmune disease but also a realistic hope to cure specific cancers, employing our own immune system in the task of fighting a tumour. We provide a structural interpretation of pharmaceutical antibodies (with Prof Cragg, Prof Glennie, Dr White, Medicine). We further have developed a novel method combining Small Angle X-ray Scattering (SAXS) and Molecular Dynamics simulation (with Prof Essex, Chemistry). 

 

Research group

Molecular and Cellular Biosciences

Affiliate research group

Computational and Systems Biology

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Articles

Lecturer

BIOL1021 Behaviour of Biomolecules
BIOL2012 Exploring Proteins: Structure and Function
BIOL3013 Molecular Recognition
BIOL3014 Molecular Cell Biology
BIOL3017 Molecular and Structural Basis for Disease
Nats3005 Research Project in the Natural Sciences
Nats3006 Drugs of the Future: Designing a Magic Bullet

 

Professional Roles

CCP4 WG2 chair 

Dr Ivo Tews
School of Biological Sciences
Faculty of Environmental and Life Sciences
Life Sciences Building 85
University of Southampton
Highfield Campus
Southampton
SO17 1BJ

Room Number: 85/4041

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