News > Recent News
Recent News

Antonio and Marianna

New Research Associates

We are delighted to welcome Dr Enas Behiry and Dr Andrew Wood to the group! Enas returns to lend her experience in dihydrofolate reductase to our enzyme mechanisms project while Andy will add LOV domain expertise to our work on genetically encoded photoswitches.

Dynamical Motions in Catalysis

Dynamical Motions in Catalysis

The Journal of the American Chemical Society has spotlit our recent communication. They conclude that our study suggests that proteins motions are not universally coupled to reaction kinetics but offers clues into the types of evolutionary trade-offs that may occur in enzymes to gain thermal stability.

Read more here.

Photoswitchable Wiki Page

Wikipedia Page

The press release circulated by the Cardiff University public relations team has inspired someone to create a wikipedia page.

Knock-in Cartoon

It's a Knock In!

The School of Chemistry web pages have higlighted our new paper on enzyme mechanisms. We show that although a particular dihydrofolate mutant has previously been termed a 'dynamic knock-out' enzyme with reduced motions on a millisecond timescale, it is better considered to be a 'dynamic knock-in' at timescales relevant to chemical reactions, as increased femtosecond time scale motions are responsible for the loss of activity.

See the chemistry website news pages for more details.

Photoswitchable Peptide Cartoon

Peptide Nanoswitches Featured

Our peptide nanoswitch project has been highlighted on the Cardiff University website news centre.

Enzyme Mechanism Cartoon

Enzyme Mechanistic Study Highlighted

The Cardiff University website has publicised our new paper in the Proceedings of the National Academy of Science (USA). The paper examines the effect of making 'heavy enzymes', synthesised to contain heavy isotopes of carbon, nitrogen and hydrogen. The effects of this heavier constitution on the rate of catalysis at dfferent temperatures are explored and matched to modelling results provided by coleagues from Bristol University.

Front cover of Molecular Biosystems

Front Cover for Peptide Nanoswitches

Our illustration was chosen for the front cover of Molecular Biosystems! The article (here) describes how photo-control of the conformation of peptides can be used to activate the first stages of apoptosis in cancer cells. The cover illustration shows molecular model cartoons depicting lit and unlit peptides whose shadows show the effect on the conformation of the peptide backbone.

Front cover of Natural Product Reports

Front Cover for Semiochemistry of Aphids

A review article written by Dr John Pickett, Professor Allemann and Dr Michael Birkett on the semiochemistry of small sap feeding insects in Natural Product Reports has been chosen for a front cover illustration.

Antonio and Marianna

New Postgraduates

We are delighted to welcome Antonio Angelastro and Marianna Loizzi to the group! Antonio will join our enzyme mechanisms research and Marianna will join our terpene cyclases project.

Learned Society of Wales Logo

Professor Allemann Elected to Learned Society

Professor Rudolf Allemann has been elected as a fellow of the Learned Society of Wales. The Society, which was formed in 2010 to represent Welsh learning, elects its fellows against the criterion of a demonstrable record of excellence and achievement in an academic discipline.

New PhD Students

Welcome back Melodi and Ryan! Both have joined the group as PhD students working on terpene cyclases and photoswitchable peptides respectively. Roger Glanville has also joined the group to work on synthesising molecules to explore the mechanisms of terpene cyclases.

New Postdoc

We welcome Dr Rebecca Salter to the group. Rebecca will be working a the BBSRC funded project entitled "Controlling cell death and proliferation with encodable visible light responsive proteins."

Encore!

Congratulations to Sarah, whose calpain poster continues to impress judges. She won second prize in the poster competition at the RSC Bio-Organic Section Forum at Leicester. Rob also gave a talk about Biophotonic Nanoswitches.

Poster Prize!

Congratulations to Sarah, whose calpain poster won second prize at the Cardiff Chemistry Conference! Rob gave the conference a short talk about Biophotonic Nanoswitches.

μ-Caplain is Front Page News

Front cover of MedChemComm

Congratulations to Sarah, whose illustration of her work on the inhibition of the enzyme μ-calpain is featured on the front cover of the new issue of MedChemComm.

μ-Calpain is linked to the spreading of white blood cells, which facilitates their leaving the bloodstream in order to reach sites of inflammation. Over-activation of μ-calpain can lead to inflammatory auto-immune diseases such as rheumatoid arthritis, making it an important and valuable target for inhibition. Our MedChemComm paper describes work with other Cardiff researchers culminating in the creation of the most potent calpain inhibitors created so far.

BBSRC Grant: Protein-ligand Coupled Motions in DHFR Catalysis

Comparison of dynamic knockout and wild type structures

The role of protein motions in enzyme catalysis is a key issue in modern enzymology. One of the most studied enzymes in this area, both internationally and here at Cardiff University in the group of Professor Rudolf K Allemann, is the dihydrofolate reductase from E. coli (EcDHFR), an enzyme that catalyzes the NADPH-dependent reduction of dihydrofolate to tetrahydrofolate. Previously, a 'dynamic knockout' mutant of EcDHFR with a reduced reaction rate was reported by groups at the Scripps Research Institute and Penn State University. It was suggested that the decreased activity of the 'dynamic knockout' was a consequence of a loss of protein dynamics, directly associated with hydride transfer.

Dr Joel Loveridge, Enas Behiry and Jiannan Guo in the Allemann group have now provided experimental data that shows that the chemistry of the reaction is essentially the same in the 'dynamic knockout' as in the wild-type enzyme. The decrease in enzyme activity is therefore not a direct result of an impairment of protein dynamics. Instead, the conformational state of the enzyme immediately prior to hydride transfer, which determines the electrostatic environment of the active site, affects the rate constant of the reaction.

These results have wide implications for our understanding of enzymatic catalysis and our ability to control biologically important molecules in vivo with applications inter alia in research, medicine, agrochemistry and green energy. The work has recently been published in Nature Chemistry.

The Cardiff High Field Facility Opens

NMR Users and the New 600 MHz instrument 3D NMR spectrum

The Cardiff High Field NMR Facility in the School of Chemistry has opened its doors on 1 March 2012. We have a range of cutting-edge high field NMR spectrometers, including a new Bruker 600 MHz NMR spectrometer equipped with a cryo-probe which will provide a highly sensitive, faster and more efficient platform that is optimised for modern NMR protocols in the physical and the life/medical sciences.

The purchase was made possible through generous funding from Cardiff University's Large Research Equipment Fund. The new machine, the most advanced high resolution NMR machine in Wales (and indeed the South West of the UK), is ideally set up for biological samples as well as small molecule analysis and as such, will benefit researchers from across the University. Other instruments include 500 MHz, 400 MHz, 360 MHz and 300 MHz spectometers, including full low-temperature and multinuclear facilities, as well as solid-state NMR. The instruments of the CHF-NMR Facility are also available to external users.

To formally mark the opening of CHF-NMRF a symposium will be held later in the year. For more information please contact Dr Rob Jenkins.

BBSRC Grant: Protein-ligand Coupled Motions in DHFR Catalysis

Enzymes are efficient catalysts that can achieve rate enhancements of up to 21 orders of magnitude relative to the uncatalysed reactions. However, despite many decades of experimentation, the precise causes of these remarkable rate enhancements are not fully understood.

A £550k grant has just been awarded by BBSRC to staff in the School of Chemistry. The award, entitled "Protein-ligand coupled motions in DHFR catalysis" was awarded to Professor Rudolf Allemann and Professor Gerald Richter in the School of Chemistry in collaboration with Dr Matthew Crump in the School of Chemistry at Bristol University.

Hydrogen transfer reactions are of fundamental importance in all biological processes. In order to understand the effects that control the speed of these reactions, motions in the enzyme-substrate complex must be taken into account. The role that enzyme motions play in the physical steps of the catalysed reaction (i.e. binding of substrates, release of products and global conformational changes) is well established. However, the influence of such dynamic motions on the actual chemistry of an enzyme-catalysed reaction is less well defined. In particular, the influence of fast motions that actively promote the reaction is a current hot topic in mechanistic enzyme catalysis.

The correlation between dynamics and enzymatic chemistry will be examined using the enzyme dihydrofolate reductase. This enzyme is required in many essential biochemical processes including the synthesis of DNA and amino acids. It is therefore a long established drug target and several inhibitors have been discovered and successfully developed as antibacterial, antimalarial and anti-tumour drugs. The increasing and inherently unavoidable problem of drug resistance together with the poor yield from screening programmes demands a rational approach to develop new inhibitors based on a thorough understanding of the mechanistic and dynamic details of the catalytic process.

New Postdoc

We welcome Dr Louis Luk to the group. Louis has joined us from the University of Chicago and will be working on the BBSRC funded project 'Protein-ligand coupled motion in DHFR catalysis'.

PhD Student Invited On RSC Delegation To India

Sarah Adams, a third year PhD student in the chemistry department under the supervision of Prof. Allemann, will represent all UK postgraduate students by touring India as part of a Royal Chemistry Society delegation.

The tour will take place at the end of January and will include scientific meetings at Guwahati, Assam where there will be a symposium held at the Indian Institute of Technology, Trivandrum in the south of India, where the 6th RSC/Chemical Research Society of India symposium will take place, followed by the 14th CRSI international conference. The centrepiece of the visit will take place in Kolkata, where a celebration of life and work of Acharya P. C. Ray on the anniversary of his 150th birthday will culminate with the RSC President unveiling the first ever Chemical Landmark award plaque outside Europe.

Sarah, the only student in the delegation, will give oral and poster presentations to demonstrate her work on the inhibition of the enzyme μ-calpain (More information) is linked to the spreading of white blood cells, which facilitates their leaving the bloodstream in order to reach sites of inflammation. Over-activation of μ-calpain can lead to inflammatory auto-immune diseases such as rheumatoid arthritis, making it an important and valuable target for inhibition. In a recent MedChemComm paper, Sarah and other Cardiff researchers disclosed the most potent calpain inhibitors created so far.

The tour of India will take place on the 29th of January until the 5th of February. For more information on the RSC events in India see here.

New Research Grant Awarded

A £440K grant has been awarded by BBSRC to staff in the Schools of Chemistry and Medicine. The award, entitled "Controlling cell death and proliferation with encodable visible light responsive proteins" was awarded to Professor Rudolf Allemann and Professor Gerald Richter in the School of Chemistry in collaboration with Prof Paul Smith and Dr Rachel Errington in the School of Medicine.

Recent work from Cardiff has shown that it is possible to induce cell death in cancer cells treated with biophotonic nanoswitches, short peptides that interact specifically with protein surfaces. In detail, the interactions between the cell cycle regulators p53/hdm-2, Bcl-xL/bak and Bcl-xL/bid depend on alpha-helices from one partner that bind into groves on the surface of the other. Peptides were synthesised with azobenzene-linkers that enable the light-controlled generation of a stable alpha-helical structure, which then interacts with the binding partner.

The objectives of the work are to develop genetically-encodable, photo-activatable proteins, which carry recognition sequences for hdm-2 and Bcl-xL in the Jalpha- helix of LOV domains to control their activity with respect to binding to hdm-2 and p53. The new system will allow visible, rather than UV- light to be the trigger, since it is less damaging and penetrates further into tissue. The work will deliver novel generic investigational tools and insights into the biology of cellular pathways with potential applications in therapy.

Read more here.

New PhD Students

Stella Matthews and Daniel Grundy have joined the group as postgraduate students this month. The whole team is looking forward to working with them.

Centre for Biomedical Photonics Established

Together with the groups of Prof Paul Smith and Dr Rachel Errington in the Cardiff School of Medicine and colleagues in Swansea, Glasgow and the School of Physics at the University of Bristol we are establishing a Centre for Biomedical Photonics (CBP). This initiative is based on the award of the EPSRC funded Basic Technology grants: Dynamic Holographic Assembler, Optical Biochips, and Intercellular Biophotonic Nanoswitches.

The CBP will be transformative in two ways: (1) stimulating new interdisciplinary research directions in an industrially important field and (2) innovative PhD training to the highest technical and academic standards.

Biomedical Photonics encompasses research areas from basic chemical a physical research, advanced microscopy and analytical spectroscopy through sensors and cell manipulation to laser diagnostics and laser therapeutics.

PhD Success for Maurizio

Maurizio Muroni has successfully defended his PhD dissertation. Well done, Maurizio!

Dr Paul O'Maille Visit - 20-Jan-11

The Allemann Lab recently hosted Dr Paul O'Maille from the John Innes Centre who gave a lecture on "Catalytic landscapes and the evolutionary origins of sesquiterpene diversity".

New Postdoc - January 2011

We welcome Dr Sabrina Touchet to the group. Sabrina has joined us from the University of Rennes and will be working on the BBSRC funded project 'The Design of Bioactive Sesquiterpene-based Chemical Signals with Enhanced Stability'.

New PhD students - October 2010

We welcome three new postgraduate students - Will Dawson, Dilruba Meah and Oscar Cascon - to the group.

Sesquiterpene Grant

We are delighted to announce the award of a research grant worth over £1 million by the Biotechnology and Biological Sciences Research Council, together with the Engineering and Physical Sciences Research Council, entitled ‘The Design of Bioactive Sesquiterpene-based Chemical Signals with Enhanced Stability’ to Prof Rudolf Allemann and Dr David Miller in collaboration with Prof John Pickett, FRS, and Dr Michael Birkett of Rothamsted Research. BBSRC-funded Rothamsted Research is the largest agricultural research centre in the United Kingdom and almost certainly the oldest agricultural research station in the world.

This study is part of our ongoing research into the chemistry and enzymology of terpenoid natural products. It is aimed at food crop protection through the application of synthetic biology to the production of semiochemicals (naturally-occurring behaviour and development modifying chemicals) for the sustainable, environmentally benign management of insect pests to manipulate the behaviour of pests affecting crop, plant, animal and human health. This award not only brings valuable research income to the group but also enhances the department’s research profile in translational research through the establishment of a new collaboration with a high profile research institute.

For more information please see our research pages.

If you are interested in joining the group to work on this project, click here.

Sesquiterpene Grant in the News!

The sesquiterpene grant (see above) has already made the news, appearing in both the South Wales Echo under the headline "Sweet-smelling £1m for research into natural scents" and the Western Mail under the headline "How Welsh scientists' study of Mother Nature's smells could create the perfect perfume" on Satuday June 26th.

Prof Allemann, along with Prof John Pickett from Rothamsted Research, appeared on BBC Radio Wales' Science Cafe programme on Saturday August 1st to discuss this work. Click here to listen (7.1 MB mp3).

Book Published

RSC Biomolecular Series Book on Quantum Tunnelling in Enzyme Catalyzed Reactions (edited by Nigel S. Scrutton and Rudolf K. Allemann) is now available. The book has been reviewed in ChemBioChem, JACS, and Chemistry World.

The purpose of the book is to introduce modern theories of enzyme catalysis to a wide audience, with particular emphasis on advanced level undergraduate and PhD students as well as early postdocs who are new to the field. The focus is therefore different to recent publications, which are geared towards established researchers in the field.

In producing an ‘early entry’ volume the aim was to introduce important and emerging aspects of tunnelling in biology to inexperienced workers and to fill the need for an educational resource that is currently unavailable.

Leading researchers in the field have contributed to make this an exciting new publication that covers most aspects of this rapidly emerging field.

Biophotonic Nanoswitches Grant

A £1.76m Basic Technology grant from the Engineering and Physical Sciences Research Council (EPSRC) for the development of 'Intracellular Biophotonic Nanoswitches' has been awarded to a team led by Prof. Allemann. Click here for more information, or here to visit our Intracellular Biophotonic Nanoswitches Group website.