51ºÚÁÏÉçÇø

Leicester Institute for Pharmaceutical Innovation collaborations and projects

Networks and collaborators

EU NETWORKS: COST 15203, 16227 & 17140 (> 50 EU participants in each network)

UK Universities (e.g. Oxford, London, Leicester, Newcastle, Nottingham, Bristol, Warwick, Loughborough)

International Universities and Research Institutes (e.g. Italy, Spain, Sweden, Romania, Germany, Denmark, Netherlands, USA)

Industry / Consulting  (e.g. AstraZeneca,  GSK, GEA Process Engineering, IS Instruments Ltd, Blue Frog Design Ltd, Ocean Optics UK, OncoLytika Ltd, Biopharma Process System Ltd, Microfresh and Pal International, Medilink)

Patient and Public Involvement Networks (e.g. East Midlands Group - Parkinson’s UK)

Funders

Beyond Batten Disease Foundation

Cancer Research UK (CRUK)

Defence, Science and Technology Laboratory

Engineering and Physical Sciences Research Council (EPSRC)

EU Horizon 2020

Innovate UK

Michael J Fox Foundation

Royal Society

Science and Technology Facilities Council (STFC)

Society for Applied Microbiology

Schwabe Pharmaceuticals

Schlumberger Foundation

Pharmaceutical Technology and Nanomedicine Research Group

Artificial pancreas (Professor Joan Taylor)

Our lab is dedicated to developing an artificial pancreas. This is an insulin-dispensing device that responds to the body to deliver variable doses as an intelligent response to the blood glucose. Instead of two to four injections into the skin at intervals throughout the day, this is a continuous supply, but one that adapts to the changing blood levels and should give better outcomes as a result. The intention is that it will be totally implantable and so nothing would be visible from the outside.

It is not yet ready for human trials but we already know it works quite well, so we are looking to develop it as soon as possible. We are actively searching for an industrial partner to do this and are also looking for ways to raise the funding needed.

We have valued public opinion on this project and have used surveys and focus groups to find out what diabetic people have to say, in addition to the technical aspects of our work.

Electrostatic Powder Flow Sensor (Professor G. Smith).

An electrostatic powder flow sensor (EPF) has been developed, which measures the electrical charges on moving particles.

The fluctuation in these charges produces an electrostatic ‘noise’ signature, the characteristics of which depend on the mass flow rate of powder and the associated input variables (that is material attributes and process parameters).

• Sensitive to material attributes and process parameters.
• Retrofit capability for a number of different processes with different flow regimes.
• Signal analysis techniques that can be used to derive process-dependent information on the powder flow behaviour.
• Non-intrusive, simple to operate and provides real-time information.

Through-vial impedance spectroscopy (Professor G. Smith)

Through-vial impedance spectroscopy (TVIS) is a novel process analytical technology for the development of freeze-drying processes and products.

The development of TVIS by 51ºÚÁÏÉçÇø, in collaboration with our partners - GEA Lyophil GmbH, Sciospec GmbH, the National Institute for Biological Standards and Control, BlueFrog Design, Sanofi-Ireland, and OncoLytika - marks the first time that impedance spectroscopy has been used to characterise materials within conventional glass freeze-drying vials, without having to insert the electrodes into the product (that is the solution under-going freeze-drying).

Chemistry for Health and Bioanalytical Sciences Research Group

Bioanalytical Science (Professor Martin Grootveld)

Professor Grootveld’s major research interests include bio- and chemometrics/metabolomics, including NMR-based exploratory data analysis and pattern recognition techniques; biomolecular investigations of the aetiology and pathogenesis of lysosomal, inflammatory, cardiovascular and oral diseases, together with cancer; biomedical, bioanalytical and metabolomics investigations of the therapeutic activities of drugs; oxidative stress and its roles in the aetiology and pathogenesis of human diseases; food toxicology, particularly the adverse health effects of dietary lipid oxidation products; the experimental design of clinical trials and statistical analysis of data derived therefrom, and research ethics.

Water Purification (Professor Katherine Huddersman)

The Water Purification Group headed by Professor K. Huddersman has developed a nanocoated surface functionalised catalyst supported on a polymer fabric for use in catalytic oxidation. Applications are to the treatment of wastewater for the degradation of toxic pollutants and with colleagues in microbiology for applications in disinfection.

She has won more than £4 million of grant funding in these areas from a number of government funding bodies, such as EPSRC, Innovate-UK, DERA, The Home Office and Schlumberger, and has a number of patents in both these areas, including industrial-scale catalyst production.

The aim of the water treatment is to provide water for re-use, either back into the industrial process from which it came or for land irrigation, so overcoming water scarcity by allowing potable water to be use for drinking purposes only. She also has a licence with a US-based company for use of the catalyst in the ophthalmic area to combat acanthamoeba, which is a rare but serious disease often resulting in blindness.

Natural Products Research (Dr R. Arroo)

Despite the tremendous progress that has been made in synthetic organic chemistry, currently 25 per cent of all prescription drugs are derived from natural sources. If we consider anti-cancer drugs only, 65 per cent of the clinically used drugs are of natural origin or are semi-synthetic derivatives of naturally occurring compounds.

Natural products research has two main lines of research - one is optimising production of medicinal compounds from natural sources, the other is on elucidating the mechanisms by which dietary phytochemicals can prevent the onset, or slow down progress of, degenerative diseases.

We have worked on the production of artemisinin - a key ingredient in the preparation of antimalarial drugs - with leading agricultural institutes and agricultural producers, for example , , and .

Research into the mechanisms of action of dietary compounds that inhibit carcinogenesis has focused particularly on flavones. These natural products are regularly referred to as phytoestrogens and share some structural features with human steroid hormones. We have shown that, depending on the substituents on the flavone core, some of these molecules can interfere with cell signalling processes and arrest cell division. Current work focuses on in silico docking of selected flavones with enzymes involved in steroid metabolism, and on the effect of dietary flavones and their metabolic products on cell signalling, and on the cell-division cycle.

Dr Federico Brucoli is a pharmacist and medicinal chemist whose research interests include cancer chemotherapy, antimicrobial drug resistance and the study of natural products as templates for future drug design. His expertise ranges from synthetic organic chemistry to bioassay-guided evaluation of anticancer and antibacterial small-molecules that are designed to interact with individual protein-targets or predetermined DNA sequences. Emphasis is also given to the isolation and structural characterisation of bio-active molecules from natural sources, including plants and marine species.

Dr Brucoli’s current research activity is focused on the rational design of anti-tuberculosis hit-molecules, with novel mode of actions to be advanced into drug-leads. His research is multi-disciplinary, falling at the interface between chemistry, biology and pharmacology, and involves extensive collaborations with colleagues in USA, UK, Europe and India.

Molecular Imprinting (Dr Nick Turner)

My research interests lie in the field of molecular recognition and in particular the development of artificial (non-biological) recognition elements. I use a technique known as molecular imprinting.

Molecularly imprinted polymers (MIPs) are a simple elegant biomimetic technology where recognition sites, analogous to the binding sites of antibodies, enzymes and receptors are created in polymeric materials containing complementary functionality to a target molecule. After preparation, cavities that are complementary to the shape and chemical profile of the target are formed, allowing specific recognition and rebinding. MIPs represent a generic, versatile, scalable and cost-effective approach to the creation of synthetic molecular receptors and are rapidly becoming commercially relevant.

My work is focused on:

1: MIPs for trace capture and analysis.

Preparation of solid phase extraction (SPE) materials for biomarkers, toxins, pollutants, explosives and pharmaceuticals analysis. This is a traditional imprinting area where polymers are used as targeted clean-up for further analytical study. I currently have research focused on anti-doping supported by the Partnership for Clean Competition, a US foundation and partner of WADA.

2: Hybrid imprinting using biological materials as monomers

The development of imprinted nanoparticles that are hybrids between aptamers (short chains of single strand DNA that have molecular recognition properties) and MIPs. These apta-MIPs maintained the best properties of both classes of materials. They demonstrated high affinity and specificity, towards their targets. In addition they addressed the stability issues associated with aptamers.

3: Macromolecule imprinting

Investigating selective rebinding of proteins for biological sample clean-up. Current work is focused on the imprinting of surface proteins on exosomes within a CRUK-supported early cancer detection, and exploring the imprinting of different isoforms of the same protein in an exploration of misfolds in secondary structure.

4: Biosensor design

Using MIPs and other recognition elements to generate next-gen biosensor platforms linking with common analytical platforms.

Photokinetics (Dr Mounir Maafi)

Our research focuses mainly on tackling a gap in the knowledge in photokinetics. This underdeveloped area of physical chemistry lacks adequate tools and methods despite the subject of photochemistry being more than 120 years old. Most often, the topic of photochemical kinetics is not considered in physical chemistry textbooks.

Our research has focused on characterisation of photomechanisms and their kinetics leading to a shift of paradigm in photokinetics. It proposes valuable tools capable of explaining all the experimental observations that have not found, so far, a rational leading to their understanding. These tools also allow many predictions that are important in technology and optimization.

In terms of applications, our methods have been applied to configure photochromes, define photodegradation properties of drugs, evaluate the effects of proteins on the photo-behaviour of molecules, and develop a new lineage of very handy actinometers.

We are also working on amending the International Council on Harmonisation (ICH) guidelines for photostability, to improve the regulatory drugs’ testing protocols.

Pharmacology and Neuroscience Research Group

Neuropharmacology.

The neuropharmacology strand is interested in the action of drugs on brain function, with particular reference to how the brain changes structurally and functionally in response to drugs used in the treatment of psychiatric disorders including depression, schizophrenia, ADHD and dementia.

For these purposes, we are using a range of molecular techniques for the investigation of genes, proteins and neurotransmitters implicated in the mode of action of psychotropic drugs, as well as in vivo electrophysiological techniques to investigate their effects on neuronal activity.

Neurobiological Disorders.

Our research on neurobiological disorders uses a wide range of molecular and cellular techniques to investigate pathophysiological mechanisms underlying the pathology of neurobiological disorders including Parkinson’s disease, Alzheimer’s disease, Niemann-Pick disease type C, schizophrenia, pain disorders, neuromuscular disorders and brain tumours. We use a range of state-of-art techniques encompassing bioinformatics, cellular and molecular biology, primary cell culture, live-cell imaging, confocal microscopy, calcium imaging, organotypic cultures, organ bath experiments, neurochemistry, animal gene knockout and behaviour models as well as in vivo and in vitro electrophysiology.

The overall aim of this research is to understand the role of brain neuronal pathways, neurotransmitter systems, ion channel mechanisms, lipids, lysosomal and mitochondrial mechanisms, autophagy signalling mechanisms, gene expression and DNA damage in the pathology of neurodegenerative and psychiatric disorders.

Pharmacology and Patient-Centred Teaching.

Members of the group are actively engaged in teaching all aspects of Pharmacology to our MPharm and Pharmaceutical Science students. In our teaching, we seek to translate the group’s vast and diverse expertise in cellular and molecular pharmacology to applied therapeutics. A novel patient-centred approach is central to the teaching of this discipline, as conceived and developed within the Leicester School of Pharmacy. The text book Pharmacology for Pharmacy and the Health Sciences was tailor-written to complement this teaching practice, and is edited by members of the research group.

Our current research focuses on the following fundamental questions:

• Why is there a delay in the onset of therapeutic effect by antidepressant drugs?
• What is the role of glutamate-dopamine interactions in the pathology and treatment of schizophrenia?
• What are the long-term effects of psychotropic drugs on the developing brain?
• What is the role of sphingolipids in antidepressant drug action?

Current high-impact projects include:

• Psychostimulants and the developing brain
• Antidepressant drugs and neuronal adaptation
• The gastrointestinal system and brain function (gut-brain axis)
• Cerebellar mechanisms of schizophrenia
• Potassium channel mechanisms in neuropathology
• Function of Niemann-Pick disease protein in lipid transport
• Compartmental stress signalling in age-related neurodegeneration
• Mitochondria quality control and Parkinson’s disease
• New generation allosteric modulators of purinergic signalling for anti-tumour therapy
• Autophagy signalling mechanisms
• Evaluation and development of the patient-centred approach to teaching pharmacology

Infectious Disease Research Group

Natural product research

Dr Katie Laird's natural product research encompasses a number of academic and industry projects. She has developed a patented antimicrobial vapour based on essential oils that decontaminates both the air and surfaces. In addition in collaboration with industry she has developed a completely natural antimicrobial facial toner for acne, which is as effective as prescription therapies in vitro. Current research includes the use of natural products and their components as adjuvants to antibiotics in order to exert a synchronised mechanism of action against antibiotic resistant strains.

Novel biocide research

Dr Walsh's research focuses on assessment of the activity and mode of action of a new and existing disinfectants. One aspect of this research has been the development 51ºÚÁÏÉçÇø's novel antimicrobial catalyst technology which has been patented and is currently licensed in one field of use. Significant improvements in the activity of hydrogen peroxide can be achieved in the presence of the catalyst which offers a potential advantage over current commercial disinfection systems. Further collaborations in this or related areas are welcome. Dr Walsh also has an interest in the possible link between biocide use and antibiotic resistance. She has published in this area and collaborates with Dr Smith and Dr Samarsinghe to investigate the underlying mechanisms involved in biocide tolerance.

Nano - metal research 

The use of a range of metals is being explored as antimicrobials against the microorganisms that cause Hospital Acquired Infections. has assessed the use of metals in a range of different shape formats in order to eradicate biofilms of clinical isolates of Staphylococcus aureus and Pseudomonas aeruginosa , the mechanisms of action of nano-metals is also being explored. 

Diagnostic research 

In collaboration with the Leicester Royal Infirmary, work involves the use of rapid technologies to detect highly antibiotic resistant Escherichia coli in urinary tract infections. A prevalence study was conducted to investigate the prevalence of antibiotic resistant urinary tract infections in the Leicestershire area. Current research includes the effect of garlic extract on the expression of genes in the biofilm; and the effect of cranberry extract on the genes that cause Escherichia coli to adhere to the urinary tract wall.  

Microbial immune evasion research

Dr Umakhanth V Girija's research is primarily focussed on molecular strategies adopted by microbial pathogens to evade the human immune system, particularly complement attack. Immune evasion by pathogens is a great challenge in treating many microbial infections. Dr Girija's lab investigates and characterizes several putative immune evasion and molecular mimicry candidates so as to provide novel insights into designing therapeutics.  With collaborations at UK and international level, a range of pathogens including bacteria (Serratia), yeast (Candida) and parasites (Schistosoma, Leishmania) are investigated. Advanced techniques such as recombinant protein production, purification, protein-protein interactions, microbial gene knock-outs, biochemical, immunological assays and natural products screening are employed to explore the challenges posed by pathogens and find novel solutions.

Transcriptional regulation in bacteria 

Dr Laura Smith's research focuses on understanding how bacteria sense the various signals associated with infection (for example oxidative stress and nitric oxide) via transcription factors and alter their gene expression accordingly, with a particular focus on those involved in the dormancy switch in Mycobacterium tuberculosis.

Healthcare laundry 

The role of textiles as a possible transmission route for Hospital Acquired Infections has been evaluated by Dr Katie Laird, she has looked a range of issues including assessing how NHS nurses adhere to the NHS domestic laundering policy, the survival of C. difficile from hospital bed sheets through industrial laundering and the ability for bacteria to withstand low temperature domestic laundering.  In addition she works on antimicrobial laundering detergents and  “Green” antimicrobial textile coatings using natural products. This work is in collaboration with the NHS, national laundries and industry.  

Efficacy of infection control products 

Dr Walsh and Prof L Goodyer have investigated the activity of commercially available travel hand rubs with the aim of developing more effective formulations. Another study is currently focusing on the efficacy of disinfection travel products for potable water. Dr Walsh has also led the microbiology aspects of randomised controlled trials investigating: the efficacy of using brushes and picks in surgical scrubbing; and the efficacy of body washing.

Emerging parasites 

Dr Peña-Fernández, in collaboration with the Parasitology and Immunology Section at the Universidad San Pablo CEU (Spain), is performing different projects to determine the presence and distribution of emerging human parasites in the urban environment of major cities in the East Midlands such as Leicester. The emerging parasites that are being studied are protozoa parasites such as Cryptosporidium and Cyclospora. The parasitology group that has been created will explore the possible zoonotic role of these parasites and their possible role in the contamination of the urban environment.  This data will be used to identify possible human health risks and develop applicable intervention measures to protect the public.

A germ's journey 

Is an interactive book and website () developed by Dr Katie Laird and Dr Sarah Younie (educationalist), the book is aimed at preschool children. Through interactive action and consequence learning, children should come to understand about the invisible germ, germs hiding and health & disease.  The Society for Applied Microbiology has supported this study and 1000 books will be used for widening participation both in the UK, India and Africa. Research is being conducted on the effectiveness of a Germ’s Journey as an educational intervention tool and a MESH guide has been written to complement the work.

Parasitology online resource 

An innovative teaching group form by biomedical scientists, parasitologists, IT developers and academics from different EU Universities (Universidad San Pablo CEU, Universidad de Alcalá and Universidad Miguel Hernández de Elche; Spain) and the UK, led by Dr Peña-Fernández (51ºÚÁÏÉçÇø), is designing, creating and developing a complete on-line package in Parasitology for undergraduate and postgraduate students that study health sciences. The “e-Parasitology” package will be accessible through the 51ºÚÁÏÉçÇø website soon in 2017 and will be focused on infection, prevention and treatment of major and emerging parasitic diseases. The e-Parasitology package will be an important teaching and learning resource for students and academics.