Chemistry researchers at The University of Warwick and the John Innes Centre, have found a novel signalling molecule that could be a key that will open up hundreds of new antibiotics unlocking them from the DNA of the Streptomyces family of bacteria.

With bacterial resistance growing researchers are keen to uncover as many new antibiotics as possible. Some of the Streptomyces bacteria are already used industrially to produce current antibiotics and researchers have developed approaches to find and exploit new pathways for antibiotic production in the genome of the Streptomyces family. For many years it was thought that the relatively unstable butyrolactone compounds represented by "A-factor" were the only real signal for stimulating such pathways of possible antibiotic production but the Warwick and John Innes teams have now found a much more stable group of compounds that may have the potential to produce at least one new antibiotic compound from up to 50% of the 1000 or so known Streptomyces family of bacteria.

Warwick Chemistry is rapidly becoming one of the best chemistry departments in the UK, as indicated by their current ranking of UK chemistry departments by the Times 2009 Good University guide 

Warwick Chemistry is heating up in becoming the top place in the UK to study chemistry with large investments in scientific infrastructure, for example £70 million under Science City in energy, translational medicine, and materials, thereby creating an impressive atmosphere for scientific research and education. 

This great environment continuously attracts many world-leading scientists to move from other top institutions, such as prof. Peter Sadler (FRS, transfer from Edinburgh, now Chair of Warwick Chemistry), Tim Jones (transfer from London Imperial), prof Peter O'Conner (Boston University, USA), Rachel O'Reilly (Cambridge University), and Giovanni Costantini (Max Planck Institute for Solid State Research, Germany).

Warwick Chemistry is currently recruiting about 120 undergraduates a year offering them world class education by enthusiastic scientists from its 5 research disciplines. Warwick Chemistry will continue to invest and expand its portfolio over the next few years with the ambition to be one of the top 3 in the UK.

A new study by research chemists at the University of Warwick has challenged a century old rule of pharmacology that defined how quickly key chemicals can pass across cell walls. The new observations of the Warwick researchers suggest that the real transport rates could be up to a hundred times slower than predicted by the century old "Overton’s Rule". This could have major implications for the development and testing of many future drugs.

Overton’s rule says that the easier it is for a chemical to dissolve in a lipid (fat) the easier and faster it will be transported into a cell. The Rule was first outlined in the 1890s by Ernst Overton of the University of Zürich. He declared that substances that dissolve in lipids pass more easily into a cell than those that dissolve in water. He then set forth an equation that predicted how fast that diffusion would happen. One of the key parameters in that equation is K which defines the lipophilicity (oil-liking nature) of the chemical. The higher the value of K, the faster the predicted cell permeation rate. For over a century, medicinal chemists have used this relationship to shape their studies and clinical trials.

Commonly used industrial dyes hold the key to advancing the new science of 'spintronics', say researchers working on a new a £2.5 million study.

Spintronics holds out the possibility of a range of future applications, such as quantum computing, which aims to deliver secure, low-power computers capable of processing much larger quantities of data than is currently possible. Scientists believe that sensitive new biosensors able to analyse blood or urine samples rapidly and accurately could also be developed as a result of this work.

The new Basic Technology grant awarded by the Engineering and Physical Sciences Research Council will support research into the magnetic properties of metal atoms found in industrial dyes such as Metal Phthalocyanine (MPc), a blue dye used in clothing. The team from the London Centre for Nanotechnology - a joint venture between Imperial College London and University College London - and the University of Warwick believes that finding ways to control and exploit these molecules will allow spintronics to be applied in new ways.

The Macro Group UK met at Warwick Chemistry for their annual Frontiers in Science Meeting in Combination with the Young Persons Research Meeting.

148 delegates from all over the UK were attending the conference which made it the one of the largest and most successful meetings the Macro Group UK ever had of this type.

Dave Haddleton, Chair of the Macro Group UK said: "To have approximately 130 polymer chemistry students from all over the UK having such a great time scientifically and socially is fantastic for UK polymer chemistry and also for Warwick Chemistry and the University"

Chair organiser of the conference was assistant professor Andrew Dove from Warwick Chemistry.

Patrick Colver, a final year PhD student in Stefan Bon's group was one of the winners of the best poster prize.

Photos of the meeting can be found here

Iron regulation

New Role For Transferrin

Blood protein forms fibers, releases rust

Rachel Petkewich

Transferrin, the blood protein responsible for transporting iron throughout the body, can assemble into fibers that release bits of rust (Angew. Chem. Int. Ed., DOI: 10.1002/anie.200705723). These unexpected findings from in vitro studies may help researchers decipher iron's role in various neurodegenerative diseases.

Howard Lightfoot and Arindam Mukherjee

Transferrin's Fe³⁺-binding site grips the metal (small orange ball) with a carbonate anion, two tyrosinates, an aspartate, and a histidine.

Diseases such as Parkinson's, Alzheimer's, and Huntington's have been associated with the defective regulation of iron in the brain. "If transferrin plays a role in accumulation of iron in brain tissue, then understanding the mechanism of this process will allow the design of drugs that could disrupt transferrin aggregation," says Peter J. Sadler, a chemistry professor at the University of Warwick, in England. Sadler carried out the work in collaboration with chemistry professor Sandeep Verma of the Indian Institute of Technology, Kanpur, and colleagues.

Their findings have intrigued other researchers. "Transferrin has never been shown to form fibrils, let alone ones with pockets of mineralized iron," says N. Dennis Chasteen, a chemistry professor at the University of New Hampshire. "Until this paper, human serum transferrin had been universally thought of simply as a transport protein for iron and other metals in blood circulation."

Transferrin is best known for transporting two Fe³⁺ ions. Each ion is tightly bound to four amino acid side chains that form a compartment and a carbonate anion that acts as a synergistic keystone.

Sadler and his colleagues deposited dehydrated transferrin on various surfaces under conditions that mimic living systems. They used microscopy techniques to show that the protein assembles into fibers and forms metal nanocrystals. Diffraction patterns indicate similarities in composition between the crystals and an iron oxide mineral called lepidocrocite. The researchers plan further experiments to see whether transferrin fibers form and iron minerals accumulate in vivo.

Researchers from the Universities of Warwick, Edinburgh, Dundee and the Czech Republic’s Institute of Biophysics have discovered a new light-activated platinum-based compound that is up to 80 times more powerful than other platinum-based anti-cancer drugs and which can use "light activation" to kill cancer cells in much more targeted way than similar treatments.

The platinum-based compound known as "trans, trans, trans- [Pt(N3)2(OH)2(NH3)(py)]", or a light activated PtIV complex, is highly stable and non-toxic if left in the dark but if light falls upon it becomes much less stable and highly toxic to cancer cells. In fact it is between 13 and 80 times more toxic (depending on how and on which cells it is used) to cancer cells than the current platinum based anti-cancer drug Cisplatin. Moreover it kills the cells by a different mechanism of action, so it can also kill cisplatin-resistant cells.

Professor Peter Sadler, Chairman of the Chemistry Department of the University of Warwick, who led the research project said:

"Light activation provides its massive toxic power and also allows treatment to be targeted much more accurately against cancer cells."

The compound could be used in particular to treat surface cancers. Patients could be treated in a darkened environment with light directed specifically at cancer cells containing the compound activating the compound’s toxicity and killing those cells. Normal cells exposed to the compound would be protected by keeping the patient in darkness until the compound has passed through and out of the patient.

The new light activated PtIV complex is also more efficient in its toxic action on cancer cells in that, unlike other compounds currently used in photodynamic therapy, it does not require the presence of significant amounts of oxygen within a cancer cell to become toxic. Cancer cells tend to have less oxygen present than normal cells.

Although this work is in its early stages, the researches are hopeful that, in a few years time, the new platinum compound could be used in a new type of photoactivated chemotherapy for cancer.

Peter Dunn, Press and Media Relations Manager,
University of Warwick, 024 76 523708
mobile 07767 655860 p.j.dunn@warwick.ac.uk

PR112 PJD 21st December 2007

The University Of Warwick has just been awarded £4 Million under the government’s Science and Innovation scheme to develop a new Centre in Analytical Science.  The Centre will develop new analytical approaches and use the very latest technology and techniques in scientific measurement and data analysis. The Centre will bring together scientists from broadly across the University to pool their expertise being led from Chemistry, but including computer scientists, physicists, life scientists, medical researchers, statisticians, and engineers.

For more information please contact:           

Professor Mark Smith, University of Warwick
Tel: 024 76 522380

Peter Dunn, Press and Media Relations Manager,
University of Warwick,  024 76 523708 or 007767 655860  
p.j.dunn@warwick.ac.uk