Mycobacterium tuberculosis......can we beat it?

London
Thursday, 21 March 2013

The venue for this event is The Royal College of Pathologists
 2 Carlton House Terrace is the home of the Royal College of  Pathologists, a professional membership organisation, concerned with all matters relating to the science and practice of pathology.

Carlton House Terrace was constructed largely between 1826  and 1829 and it remains the property of the Queen.   Its balconies overlook the Mall in central London where Buckingham palace stands.

This is a Euroscicon Small Conference, an outline of the day can be found at 
www.euroscicon.com/EurosciconMeetingStructure.pdf

Mycobacterium tuberculosis......can we beat it?
Thursday, 21 March 2013 09:00 - 17:15

The Royal College of Pathologists
2 Carlton House Terrace
London
SW1Y 5AF
United Kingdom

Mycobacterium tuberculosis is one of the most successful human pathogens.  Treatment of tuberculosis requires a long duration time with the use of multiple drugs. There is also an alarming emergence of multidrug resistant M. tuberculosis. As a result a need have arisen to develop novel anti-tubercular agents. This EuroSciCon meeting will present cutting-edge research on developments in the detection and treatment of tuberculosis.



This event  has
CPD accreditation and will have a  discussion panel session.  


On registration you will be able to submit your questions to the panel that will be asked by the chair on the day of the event

 

Meeting Chair:   Dr. Sanjib Bhakta, Head of Mycobacteria Research Laboratory, Institute of Structural and Molecular Biology, Birkbeck, University of London & UCL Research Department of Infection.

9:00 – 9:45           Registration

 

9:40 –10:00          Introduction by the ChairDr. Sanjib Bhakta

Birkbeck, University of London, London , United Kingdom


 
An integrative approach in targeting different physiological stages of Mycobacterium tuberculosis. Dr Sanjib Bhakta, Head of Mycobacteria Research Laboratory, Institute of Structural and Molecular Biology, Birkbeck, University of London & UCL Research Department of Infection



10:00 – 10:20      Mycobacterium tuberculosis in the Moonlight: The Unusual Preponderance of Moonlighting Proteins Used by Mycobacterium tuberculosis as Virulence Factors
Professor Brian Henderson, Eastman Dental Institute, London, UK
Protein moonlighting defines a recently recognised property of some proteins to have more than one unique biological function.  Evidence is emerging that moonlighting proteins can play a role as bacterial virulence factors with a growing number of human pathogens.  Most pathogens identified as having moonlighting proteins generally have only one, or at most two, such molecules.  In contrast, at the time of writing, M. tuberculosis has 12 of its proteins functioning as moonlighting molecules each playing a potential, or identified, role in the virulence phenotype of this organism.  Examples include the antigen 85 complex proteins which function both as mycosyltransferases and as ligands for the major host component fibronectin.  Binding to fibronectin is a well-recognised method for bacteria both to adhere to the host and also to invade host cells.  The cell stress protein, chaperonin 60.2 is found on the cell surface and functions as an adhesin and invasin by binding to the host cell receptor CD43 on macrophages.  The paralogous protein, chaperonin 60.1, plays a major role in the generation of the multinucleate giant cells found in the tuberculoid granuloma, but appears not to be an adhesin.  These chaperonins also have major effects on macrophage activation. The role of the various mycobacterial moonlighting proteins in tubercular disease will be described, and their potential as therapeutic targets will be explored

 

10:20 – 10:30 POLYTB: A genome-browser web tool to investigate m. tuberculosis genetic polymorphisms derived from next generation sequencing data

Francesc Coll, Mark Preston, Kim Mallard, Ruth McNerney, Nigel Martin, Taane Clark

London School of Hygiene and Tropical Medicine, London, UK; BirkBeck College, London, UK

 

10:30 – 10:40   Investigation of the structural contributions to the antimicrobial peptides activity against Mycobacterium tuberculosis

Y Lan, WC Yam, AJ Mason and JKW Lam*

 Department of Pharmacology & Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 2/F,  Laboratory Block, 21 Sassoon Road. Hong Kong

10:40 – 11:00      Speakers’ photo then mid-morning break/networking , trade show and POSTER SESSION 1

                                Please try to visit all the exhibition stands during your day at this event.  Not only do our sponsors enable Euroscicon to keep the registration fees competitive, but they are also here specifically to talk to you

11:00 – 11:20       New approaches to sputum analysis; implications for treatment and transmission
Professor Mike Barer, Professor of Clinical Microbiology, University of Leicester, UK


11:20  – 11:40      Simple diagnosis of TB infection
Christopher GrangerDirector, Global Professional Relations, 
Oxford Immunotec Ltd, Abingdon,United Kingdom
The T-SPOT.TB test identifies TB infection. Guidelines in many countries indicate its use in preference to the tuberculin skin test in many of the following patient groups:

•               Contact tracing

•               Healthcare workers

•               HIV patients

•               Immuno-suppressed patients, including pre-TNF screening

•               New Entrants

•               Hard-to- reach groups, including prisoners

The design of the test ensures it has excellent sensitivity and specificity. Additionally the simple phlebotomy and robust assay methodology allows the test to be carried out easily and simply in all these patient groups.

 

11:40- 12:00         How we can use drugs to treat tuberculosis better

Professor Stephen Henry Gillespie, University of St Andrews, Scotland

There is a growing body of research at preclinical and clinical stages investigating new drugs and regimens for the treatment of tuberculosis.  We have also learned much about the differing cell states of tuberculosis and how they pose a challenge to treatment.  This talk will summmarise some of thie key new data in the area and attempt to indicate what the challenges are to much shorter treatment regimens and how these might be achieved.

 

12:00 - 12:10        A new approach for fast diagnosis of tuberculosis using gas chromatography-mass spectrometry and chemometrics

NA Danga,*, S Kuijpera, E Waltersb, M Claassensb, D Soolingenc, G Vivo-Truyolsa, HG Janssena,d , AHJ Kolka

Analytical Chemistry & Forensic Science, University of Amsterdam, Science Park 904, 1098 XH Amsterdam, The Netherlands

 

12:10- 12:20 Development of aminocoumarins as a new class of potential drug candidates against multi-drug resistant tuberculosis (MDR-TB)

R. Tandon, P. Ponnan, K. Garima, N. Aggarwal, M. V. Basil, M. Nath, V.S. Parmar, H. G. Raj, A. K. Prasad, M. Bose

Department of Microbiology, V. P. Chest Institute, University of Delhi, India

 

12:20- 12:30 Genes mutations of Drug-Resistant, (Rifampicin, Isoniazidr and Fluoroquinoloner), Mycobacterium tuberculosis from TB patients in Thailand

Pannamthip Pitaksajjakul, Dhruba Kumar Khadka, Pongrama Ramasoota

Faculty of Tropical Medicine, Mahidol University 420/6 Rajwithii Road, Bangkok, Thailand

 

12:30  – 13:30      Lunch/networking and trade show

                                This is also a good time to fill out your feedback forms and any questionnaires

 

13:30 – 14:20       Question and Answer Session

Delegates will be asked to submit questions to a panel of experts.  Questions can be submitted before the event or on the day

 

14:20 – 14:40       Development of immune-based diagnostics for TB in a TB-endemic setting

Jayne Sutherland, Acting Head of TB Immunology, MRC Unit, The Gambia

One of the major roadblocks in reducing TB transmission is the lack of fast and accurate diagnostic tests for use in resource-poor settings. We analysed Mtb-antigens stimulated blood samples from TB suspects using a 13-plex cytokine assay. Our results indicate increased sensitivity when analytes are combined with sCD40L, IL10 and TGFα resulting in 89% correct classification of TB. Following verification in genetically diverse populations (including stratification based on strain of infection, bacterial load, HIV status and location) these will subsequently be used to develop a rapid, lateral-flow based test for screening of TB in resource-poor, TB-endemic settings.

 

14:40- 14:50 Monitoring early host responses associated with starting effective tuberculosis treatment

AL. den Hertog, AF. de Vos, PR. Klatser, RM. Anthony

Royal Tropical Institute, KIT Biomedical Research, Meibergdreef 39 1105 AZ Amsterdam, The Netherlands

 

14:50 – 15:00 Mangosteen extract coated pre-filter could inhibit aerosol M. tuberculosis

Natthakarn Tipkrua, Sunit Suksamrarn,b Pannamthip Pitaksajjakul, and Pongrama Ramasoota.

Faculty of Tropical Medicine, Mahidol University 420/6 Rajwithii Road, Bangkok, Thailand

 

15:00 – 15:30      Afternoon Tea/Coffee, networking, trade show and POSTER SESSION 3

 

15:30 – 15:50       Mycobacterium tuberculosis – new ideas, new drugs and new vaccination strategies

Professor Graham BothamleyHomerton University Hospital, London, UK
Effective short-course (6 month) treatment for tuberculosis has been available for almost 30 years.  The failure to contain this problem is largely one of health care delivery.  To short-circuit this problem, we need drugs which reduce the time required for effective treatment and vaccination strategies which prevent latent TB developing into infectious smear-positive disease.  An understanding of latent tuberculosis is essential for both targets.  M/XDR-TB offers an opportunity to test bactericidal drugs to replace isoniazid and drugs which act on slowly dividing populations of bacilli to replace rifampicin.  Genomic and proteomic studies permit an examination of latency in Mycobacterium tuberculosis.  New immunological tests offer the opportunity to examine markers of latency and reactivation.  

                                                                                                                     

15:50 – 16:10       Targeting the cell wall of Mycobacterium tuberculosis
Dr Luke Alderwick, Director of the Birmingham Drug Discovery and Screening Facility, University of Birmingham, UK

The D-arabinan-containing polymers arabinogalactan (AG) and lipoarabinomannan (LAM) are essential components of the unique cell envelope of the pathogen Mycobacterium tuberculosis. Biosynthesis of AG and LAM involves a series of membrane-embedded arabinofuranosyl (Araf) transferases whose structures are largely uncharacterised, despite the fact that several of them are pharmacological targets of ethambutol, a frontline drug in tuberculosis therapy. Recently, benzothiazinone (BTZ) inhibitors have shown nanomolar potency against both drug-susceptible and multidrug-resistant strains of the tubercle bacillus. However, their proposed mode of action is lacking structural evidence. This talk will cover some recent advances regarding the biosynthetic pathways leading to cell wall assembly including a report on the crystal structure of the BTZ target, a FAD-containing oxidoreductase M. tuberculosis DprE1, which is essential for viability. These results mark a significant step forward in the characterisation of a key TB drug target.

16:10 – 16:30       Novel targets for  tackling M. tuberculosis inside macrophage
Professor Edith Sim, Dean of the Faculty of Science Engineering and Computing at Kingston University, Kingston University, Surrey, UK

                             

16:30 – 16:50       Biomarkers for monitoring TB treatment
                                Professor Timothy McHugh, Centre for Clinical Microbiology, UCL, UK

 

16:50 - 17:00        Chairman’s summing up

 

 

Dont forget to sign up to Euroscicons’ e-newsletter at www.euroscicon.com/signup.htm to keep up to date with European Life Science news and events and to be notified of the follow up to this event

 

 

About the chair
Sanjib Bhakta’s continued research interest (currently funded by Medical Research Council, UK and Austrian Research Fund, EU) is focused on developing novel therapeutics to tackle persistence and drug resistance in Tuberculosis (XDR-TB, a global health emergency).  He has published more than 25 original research articles in last 10 years for a number of internationally acclaimed journals including J. Exp. Med., JBC, Tuberculosis, Biochem. J., J. Antimicrob. Chemother., FEBS J. and Mol. Microbiology.

Following a BSc (Hons), an MSc and a PhD in Molecular Biology & Biochemistry from world class Universities & Research Institutions in India, Dr Bhakta joined the Oxford University Department of Pharmacology in 2001 as an ISIS innovation Senior Research Scholar and shortly after he was awarded with a Wellcome Trust International Travelling Fellowship.  He graduated from The Queen’s College, University of Oxford in 2005 completing a second doctoral degree (DPhil) and received a “Sir William Paton Prize” for the best PhD presentation in Pharmacology. In 2006 he attained his first academic appointment at Birkbeck as a University Lecturer to lead his research and teaching.  To date, he has supervised five PhD students, all of them completing their degree within four years, and he is supervising a number of UG/PG project students, three PhD students, two post-doctoral scientists and a UNESCO-L’Oreal International Fellow in his Laboratory.  He became a Fellow of the Higher Education Academy, UK after achieving a post graduate certificate in Teaching and Life Long Learning in Higher Education (PGCHE) from the University of London in 2008.

He is a core member of Tuberculosis Drug Discovery-UK (http://www.tbd-uk.org.uk), the Institute of Structural and Molecular Biology, NIMR/Birkbeck/UCL and an affiliated academic Fellow of the Centre for Infection, Immunity and Disease mechanism, Brunel University.  He is a member of a number of international societies and a review Editor for the Frontiers in Infectious Diseases.  He was elected as a Fellow of the Royal Society of Medicine in 2008 and recognised as a Chartered Biologist in 2011.



About the speakers

Brian Henderson is Professor of Biochemistry at UCL's Eastman Dental Institute and is one of the early discoverers that bacteria secrete molecular chaperones which signal to host cells.  This has led on to the thesis that bacteria use their molecular chaperones as secreted moonlighting proteins which aid in the process of bacterial virulence.   

 

Stephen Gillespie has worked in Kenya researching the relationship between malaria and lower respiratory tract infection and the prevalence of parasitic infection in children in Kilifi, Kenya. He has investigated a cholera epidemic and vaccine failures in Guerrero, Mexico. He has been working in collaboration with colleagues at Kilimanjaro Christian Medical Centre since 1988 where he has, variously, studied respiratory and parasite diagnostics and novel antimalarials, anti-helminthics and anti tuberculosis agents. His main research activity is in the area of tuberculosis drug development. For the last twenty years Stephen Gillespie has been involved in various aspects of  tuberculosis drug development. This has included the evaluation of new candidate antituberculosis agents in vitro. This work has expanded into studies of the molecular mechanisms of resistance and the development of model systems to measure the fitness deficits found in resistant strains. He has been involved in the development of fluoroquinolones for tuberculosis having performed early bacterial activity studies and clinical trials of ciprofloxacin. More recently he has led the group working on the clinical development of moxifloxacin in collaboration with the Global Alliance for TB Drug Development as Chief Investigator of the REMox TB study. He is also one of the three Chief Investigators of the PanACEA consortium that is developing Europe and Africa's clinical trials capacity.

 

Graham Bothamley is a clinician experienced in the management of tuberculosis with a keen interest in translational research.  He is Chair-elect of the Tuberculosis Network European Trialsgroup (TBNET, http://www.tb-net.org/).  He is a member of the Stop TB Proposal Review Committee.  He has published >75 papers in tuberculosis, recently addressing the clinical problems of M/XDRTB in Europe, the role of immunodiagnostic tests, TB control programs in the UK and the detection of latent TB in people living with HIV, a randomized controlled trial of vitamin D in TB and the potential diagnostic value of exhaled breath.  He graduated from Pembroke College, University of Oxford in 1980 and gained a PhD in the immunology of TB from work undertaken at the MRC Tuberculosis and Related Infections Unit from 1985-88. 

 

Edith Sim studied Biochemistry in Edinburgh University graduating in 1973. She then carried out her D. Phil. using the then new technique of 31PNMR of membrane phospholipids under the supervision of Charles Pasternak in the Biochemistry Department in Oxford. After 2 years as a Royal Society Exchange Fellow at the Centre d'Etudes Nucleaires in Grenoble studying hydrogen production in Pseudomonas aeruginosa she returned to Oxford, firstly as a Demonstrator in the Biochemistry Department working in collaboration with Bob Sim on immune system proteins of the complement system. A seminal paper on the study of the mechanism of activation of complement components C3 and C4 was the basis for a study on Hydralazine induced autoimmune disease, as a Wellcome Trust senior lecturer in the Pharmacology Department. The work in turn led to investigation of the pharmacogenetics of arylamine N-acetyltransferases (NATs) and development of understanding of these enzymes in animals and also in bacteria, identifying their mechanism of action. One NAT isoenzyme in humans (NAT1) is a breast cancer marker and she has developed specific ligands along with colleagues Steve Davies and Angie Russell which change colour on binding to human NAT1.She investigated NAT in mycobacteria and showed that the NAT protein along with other gene products of the same operon are good targets for anti-tubercular therapy. Research Interests:  Currently working on a series of enzymes known as azoreductases.

Luke Alderwick is a Lecturer in Molecular Microbiology in the Institute of Microbiology and Infection (IMI) at the University of Birmingham. His many research interests revolve around understanding the biochemistry and molecular genetics of cell wall assembly in Mycobacterium tuberculosis. In close collaboration with Prof Gurdyal Besra and Dr Apoorva Bhatt, Dr Alderwick forms a trio of Principle Investigators heading one of the worlds leading academic research groups studying mycobacterial biochemistry, genetics and molecular microbiology. He is also the Director of the Birmingham Drug Discovery and Screening Facility (BDDSF), which is a new £700k high-throughput screening facility within the IMI designed specifically to allow academic-led translational drug discovery research, particularly in the area of discovering new anti-infectives.    


Chris Granger has a graduate degree in pharmacology and a masters degree in business administration. He has spent the last 10 years developing the use and application of the T-SPOT.TB test throughout the world. He has been responsible for planning and running the clinical studies that were used to obtain regulatory approvals for the test and for providing data to many Guideline Development Groups.

Jayne Sutherland completed her PhD in cancer immunology at Monash University, Melbourne, Australia. She spent 2 years on further cancer research at UCL, London before moving to the Medical Research Council Unit in The Gambia in 2006. She is currently acting Head of TB research involved in the TB case-contact platform for vaccine research, diagnostic development, childhood tuberculosis and protective biomarkers for TB.  Other projects include HIV-TB co-infection, Mtb antigen-diversity, Mtb strain differences (m. africanum), pleural TB diagnostics and BCG vaccine immune profiles.

Stephen Gillespie is the foundation Sir James Black Chair of Medicine at the University of St Andrews.  He is currently the Chief Investigator of the REMoxTB project that is investigating two treatment-shortening regimens in a regulatory pivotal study.  This study is recruiting patients throughout the world and, if successful, will support a four month treatment for tuberculosis.  Professor Gillespie is also one of the three Chief Investigators for the PanACEA consortium which is funded by EDCTP and is the main European-African clinical trials network.  He is also the Chair of TB-Drug development UK which brings together researchers from throughout the UK from medicinal chemists to clinicians.  His current work in St Andrews is to develop new and more comprehensive mathematical models of tuberculosis treatment and investigating novel approaches to identify differing tuberculosis cell cycle by non-invasive methodology.

 

This meeting was organised by Euroscicon (www.euroscicon.com), a team  of dedicated professionals working for the continuous improvement of technical knowledge transfer to all scientists. Euroscicon believe that they can make a positive difference to the quality of science by providing cutting edge information on new technological advancements to the scientific community.  This is provided via our exceptional services to individual scientists, research institutions and industry.



Keywords: TB, latent, infection, diagnosis, IGRA,Latent TB; M/XDRTB; genome; proteome; immunome, cell wall, arabinogalactan, drug discovery, benzothiazinone, tuberculosis; treatment; biomarkers; antibiotics, mutation, rpoB, gyrA, gyrB, katG, inhA, Rifampicin resistance, Fluoroquinolone resistance, Isoniazid resistance, Mycobacterium tuberculosis, Thailand, Mangosteen extract, Antimycobacterial activity, air filter, pre-filter

 

 

Registration Web Site:  www.regonline.co.uk/tb2012

 

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