Professor Les Baillie

Publication

• Date
• Type

Research

PhD Studentship Opportunity - GW4 BioMed Doctoral Training Partnership

An exciting new PhD studentship opportunity (beginning in October 2019) supervised by Professor Les Baillie is now open to applications:

A biosensor for the rapid detection of antibiotic resistant tuberculosis in nomadic African populations

Tuberculosis infects one third of the world’s population. This project will advance the development of a real time (15 min), portable, low cost, simple to use assay capable of diagnosing the disease in remote locations in Africa. This is a unique opportunity to work with engineers, biologists and clinicians to reduce human suffering.

Please contact Professor Les Baillie for further details regarding the project.

Research interests

Evolution, ecology and the role of bacteriophages in horizontal gene transfer

My working hypothesis is that B. anthracis evolved from a strain of B.cereus through the horizontal acquisition of virulence factors from other bacilli. Using a number of molecular approaches, we have generated considerable data in support of this hypothesis. The presence of conserved prophages in the genome of every isolate of B.anthracis examined to date (>300 isolates) points to phages, in addition to plasmids, playing a role in gene transfer and evolution. Our recent isolation of phages capable of infecting B.anthracis and other members of the B.cereus group will enable use to determine the environmental conditions under which gene transfer occurs

Detection of Anthrax

Given the threat posed by B. anthracis in the context of Bioterrorism there is an urgent need to develop detection assays capable of detecting spores in the environment and diagnosing infection. An ideal assay would be highly specific, could be used with minimal sample preparation and little if any support equipment, give rapid results in <60 sec, be highly stable at room temperature and could be used repeatedly. In collaboration with colleagues in the department of Microbiology and Immunology, University of Maryland in Baltimore we are working to develop thermal stable single chain antibodies from sharks for the detection of anthrax spores and toxin. Shark produced antibodies have been shown to maintain there antibody binding capacity following prolonged heat treatment thus raising the possibility of developing extremely stable assays (Stanfield et al., 2004). In collaboration with Dr Chris Geddes, a fellow faculty member at MBC we are also developing assays based on metal enhanced flourescence which can detect nanogram levels of anthrax biomarkers in human blood in as little as 30 seconds.

Pathogenecity of Anthrax

I have a particular interest in understanding the cellular event following the infection of macrophages by B.anthracis spores. My recent data suggests that even though the spore triggers a number of pathogen pattern recognition receptors, it is still able to ameliorate antibacterial killing mechanisms such as nitric oxide. Following successful intracellular germination the organism expresses a complex network of virulence factors which enable it to escape from the cell. I have a long term interest in understanding the mechanisms which regulate in vivo virulence factor expression and am currently investigating the role of the inducible PlcR virulence regulon with leading US and Russian researchers based at the NIH campus in Bethesda, Maryland.

Anthrax - Host immune responses

Understanding the immune response of immunized and infected individuals as a means of identifying mechanisms of protection. In collaboration with clinicians in Turkey where anthrax is endemic, we have characterized the immune response of infected and immunized individuals, and have shown antibodies to be the key mediator of protection. I am scientific advisor to two international companies currently developing antibody based therapies. I am also investigating the role of human memory B cells with colleagues at Emory Medical School in Atlanta. In a related effort I am working on a project with the UK MOD to optimize the immunization schedule of the UK vaccine. Finally I am a collaborator in a multi-national US NIH funded project lead by Imperial College, London to develop DNA vaccines expressing B and CD4 T cell epitopes which confer protection against anthrax and plague.

Vaccines against Anthrax

The development of vaccines against anthrax has been a central strand of my research career. I have developed two anthrax vaccines, one based on recombinant protein (UK MOD) and the other a DNA vaccine (US Navy) both of which have progressed to clinical trials. My current effort is focused on developing needle free vaccine delivery platforms such as micro-encapsulation and attenuated strains of Salmonella capable of conferring protection following oral dosing.

Therapeutic antibodies

Preformed antibodies can confer instant protection against infectious agents. Working with colleagues in Holland we have successfully isolated human monoclonal antibodies from immunised humans and demonstrated their ability to confer protection in animal models. In addition we have developed plant based systems which express human antibodies as a low cost production system.

Current students

• Dr Evans Ahorter
• Ms Phoebe Nicklin

Past students

Mr James Blaxland BSc -January 2011 - December 2014

A joint project between Pharmacy and ProTEM ServicesHops as a potential treatment for bovine tuberculosis and greenhouse gases  Tuberculosis is caused by the bacterium Mycobacterium tuberculosis and is responsible for more deaths than any other single bacterium, a close relative Mycobacterium bovis is responsible for bovine tuberculosis the animal equivalent, which in some cases can spread to humans through contaminated milk products. The disease threatens agricultural production and can have a dramatic effect on food supplies and rural communities in Wales and the rest of the UK, the Welsh assembly government recently released statistics showing that the cost to the taxpayer in compensation to cattle keepers has topped £100 million in the last 10 years. Indeed, the Welsh rural affairs minister Elin Jones showed that between January and October 2010, 6,587 cattle were slaughtered in Wales because of bovine TB.

Miss Jennifer Hawkins BSc - October 2011 - October 2014

As part of Jenny Hawkins PhD we developed a DNA based method which allowed us to identify the plants which had contributed to the making of a particular honey sample.   Once developed we employed this method on honey samples which we had previously shown contained plant derived antibacterial compounds. We were thus able to identify the plants which were the original source of the compounds and thus target them directly as a source of novel compounds.  A spin out of this work has been the identification of plants which are visited by bees and as such could be considered bee friendly.  We are currently using this information to support a number of projects across Cardiff to plant bee friendly plants which includes the  roof of the St Davids shopping centre.  See Jennifer's publication below:

Hawkins, J. et al. 2015. Using DNA metabarcoding to identify the floral composition of honey: a new tool for investigating honey bee foraging preferences. PLoS ONE 10(8), article number: e0134735. (10.1371/journal.pone.0134735)

A joint project between Pharmacy and the National Botanical Gardens of Wales. Sponsored by the Knowledge Economy Skills Scholarships (KESS).  Apothecary Bees, using the honey bee as a tool for drug discovery - BBC Report

The earliest evidence of humans collecting honey is a cave-painting in Valencia, on Spain's eastern coast, thought to date from around 8000 BC. Since about 4000 BC, the ancient Hindi medical theory of Ayurveda outlined honey's medicinal qualities in treating burns, allergies and infections. Western cultures have eventually caught up by devising honey-based wound dressings and oral medicines. But the composition of honey varies greatly, and it depends on the local flora in the bees' immediate environment. With the various flowers bees visit making honey with different healing properties the scope for finding new uses for honey is vast. At Cardiff University I will be carrying out research in order to see if honey can help fight hospital acquired "superbugs", the deadly bacteria that have developed resistant to conventional antibiotics.My study will make use of samples provided by honey-makers across the country along with a list of plants near their beehives. Raw, unprocessed samples will be vigorously screened using tests developed over the course of the three years. These tests which include agar diffusion, broth dilution and time-kill assays will be used to identify the honeys with the most activity. The KESS funded project will involve testing the effects of honey against two of the most common hospital acquired infections antibiotic-resistant bacteria MRSA and Clostridium difficile.

Miss Lovleen Tina Joshi BSc - October 2008 - September 2011

A bedside, real time detection assay for Clostridium difficile in the faeces of hospitalized patients.

The aim of this PhD is to design an assay for detection of Clostridium difficile spores and vegetative cells within >60 seconds in the faeces of hospitalised patients. There are currently few detection methods that rapidly detect C. difficile's two toxins with both high specificity and sensitivity. Thus the proposed diagnostic device will detect both virulence toxins A and B in the organism using the novel platform technology of Microwave- Accelerated Metal-Enhanced fluorescence (MAMEF). This will be achieved by identifying conserved genetic signatures from the two toxins and engineering them into the detection assay. The detection device will aid clinicians in diagnosis and treatment of patients with C. difficile infection and those patients with the potential to develop infection.

Mr Abdullah Alyousef MSc - April 2009- March 2012

The isolation and characterization of lytic bacteriophages for the treatment of Clostridium difficile.

Bacteriophages (viruses the specifically target bacteria) have been successfully used for decades in the former Soviet Union to treat infectious diseases, often in preference to antibiotics. In contrast western countries have traditionally employed antibiotics to treat similar infections and as a consequence we have seen the emergence of micro-organisms such as Methicillin resistant Staphylococcus aureus (MRSA) which are resistant to the majority of commercially available drugs. The problem of drug resistant super-bugs in our hospitals has prompted researchers to look again at the utility of employing bacteriophages (phages) to treat infections caused by these organisms.

We propose to identify phages capable of targeting and inactivating Clostridium difficile, the causative bacterial agent of a debilitating gastric infection of hospitalized patients which has been responsible for significant morbidity and mortality amongst patients in Wales. The estimated annual healthcare costs of C.difficile associated diarrhoea (CDAD) to Wales exceeds £10 million with the highest numbers reported from general and geriatric medical specialties. While the use of certain antibiotics is known to trigger infection, a contributing factor to the increased incidence amongst hospitalized patients has been the ability of the bacterium to form spores which enable the organism to remain viable for many months on contaminated hospital surfaces event following detergent-based cleaning. A 1996 study reported 20% of environmental samples taken from Cardiff hospital wards were positive for C. difficile. This is an important observation given that environmental isolates have been incriminated in the spread of CDAD via healthcare personnel hands.

The ability to treat critically ill individuals and to decontaminate their immediate environment and thus prevent the spread of infection to fellow patients would have a significant impact on healthcare outcomes and ultimately costs. Phages offer a number of advantages which include safety, they are one of the commonest life forms on the planet with a long history of safe use in humans, specificity in that they target a single type of microorganism leaving other beneficial bacterial untouched and finally they have activity against antibiotic resistant strains.

Miss Harsha Siani BSc - October 2008 - September 2011

Research Scientist and Lab Manager
A joint project between the Welsh School of Pharmacy, Cardiff University and IQ Corporation NL to develop an antibody based therapy for Clostridium difficile

Clostridium difficile has emerged as the most frequent cause of nosocomial diarrhoea, costing the US health care system $1 billion annually and the NHS £4000 to treat per case. The estimated annual healthcare cost of C. difficile associated diarrhea (CDAD) to Wales exceeds £10 million. More disturbing than the economic impact of the infection is the global year-on-year rise in the number of CDAD cases, and the emergence of a new hypervirulent strain responsible for large outbreaks of increased severity in Europe and North America.

Mr William McCully MRPharmS - January 2010 - January 2013

A joint project between the Welsh School of Pharmacy, Cardiff University and the National Botanical Gardens of Wales. Sponsored by the KESS program.  A Natural Therapeutic for the Hospital Based Pathogen Clostridium Difficile

Tea is a hot water infusion of the leaves from the Camellia sinensis plant. It is one of the most widely consumed drinks worldwide and in the UK we drink more cups of tea per head than any other nation. There are many different varieties of tea, the most common being black tea and green tea. However, these different varieties are all from the same plant and only differ by the manner in which the plucked leaves are processed.For centuries tea has been widely used for its medical properties, particularly in Chinese medicine. In recent scientific research tea has been shown to have antibacterial, anticancer and antiviral properties. These properties are thought to be due to a group of antioxidants in tea called polyphenols. Recently at the Welsh School of Pharmacy we discovered that tea inhibits the growth of the hospital 'superbug' Clostridium difficile.

The aim of my project is to try and discover what components in tea are responsible for its antibacterial activity against Clostridium difficile and to understand its mechanisms of action. I will also try to modify the growth conditions of a small plantation of Camellia sinensis plants currently housed at the National Botanical Gardens of Wales to produce a 'super tea' rich in polyphenols and high in antibacterial activity. We hope to be successful in producing a naturally enhanced tea that will be clinically effective against Clostridium difficile infection.

Teaching

MPharm undergraduate teaching

• PH1122  The role of the pharmacist in professional practice
• PH2112  Principles of drug design
• PH3202  Research methodology
• PH4116  Pharmacy research or scholarship project
• PH4117  Pharmaceutical sciences, pharmacy practice and the population

Biography

Supervisions

Current supervision

Khalid Alyahya Alyahya

Tawfiq Juraybi