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Academic and Community Activity of Dr Ahmed Member, PLoS International Advisory Group |
| Popular highlights of our activity History debugged: Down to Earth Magazine Birth place of Tuberculosis: New Scientist (London) Birth place of TB: The Times of India (Delhi) The bug's revenge: The Telegraph (Kolkata) Genome of M. indicus: Wall Street Journal |
| Dr Niyaz Ahmed is an academic bio-scientist, veterinarian and an Open Access advocate based in Hyderabad, India. He was graduated in Veterinary Medicine in 1995 and obtained further degrees in Animal Biotechnology (MS) and Molecular Medicine (PhD). Niyaz joined the Centre for DNA Fingerprinting and Diagnostics - Hyderabad, as a tenured Faculty Member (Staff Scientist) in 1998 and since then contributed a significant body of applied research in the area of infectious disease biology and genetics. Amidst his busy research career Niyaz is an ardent supporter of the PLoS lead contemporary approach to Open Science, Open Access to Science and Open Evaluation of Science. He is a Section Editor (Microbiology and Genomics) of PLoS ONE and has overseen/handled peer review of dozens of landmark articles there. Dr Ahmed is the co- founder of the ISOGEM, a scientific society headquartered at Sassari, Italy and serves as its General Secretary. He is also the co-principal investigator of the Mycobacterium w (Mycobacterium indicus pranii) genome program - India's first whole genome sequencing project. Dr Ahmed is one of the Faculty Members of the Faculty of 1000 Biology, the next generation literature evaluation and awareness service for biology and medicine. Lay summary of the research theme Research interests in our laboratory constitute analyzing trends in genomic diversity of bacterial pathogens with reference to evolution of survival mechanisms, metabolic machinery and virulence apparatuses etc. and their impact on dissemination dynamics, invasion, persistence, signaling events, molecular pathogenesis, strain evolution and prevention measures. Pathogen genome is analyzed through decipherment of genomic and proteomic diversity as a function of flexibility in gene content (plasticity zones, large deletions), gene order (transposition), and gene regulation (allelic variation, synonymous substitutions, strand displacements), possibly aimed at evolution of fittest genotypes, corresponding to changing host niches and the environment. To address these issues our group uses a host of genomic and cellular microbiology approaches. Currently, five broad based and long-term objectives are under investigation: 1) How bacterial virulence evolves as a function of genome plasticity under different compulsions offered by a colonized niche? 2) how is bacterial genome fluidity regulated? 3) what environmental stimuli are responsible for this fluidity; 4) what is the in vivo relevance of bacterial genome fluidity; and 5) how can bacterial genome fluidity be exploited for the generation and selection of optimally adapted microorganisms? Current research projects Pathogen survival tactics: Although Helicobacter pylori has been connected to gastric cancer, it has never been seen as a big threat to human health in the South Asian countries and particularly in India. This prompted us to look into the population structure of H. pylori in India. We found that it shares genetic origins as well as its trajectory of virulence genes with the western strains (Devi SM et al., 2007. BMC Genomics 8:184). A series of putative virulence factors which are also abundant in Indian isolates, were characterized by our group including those from the core (Hussain et al., 2008. PLoS ONE 3:e1481) and the flexible genome compartments (Rizwan et al., 2008. J Bacteriol. 190:1146-1151). Important among these are the virulence factors encoded by the genomic plasticity region genes which constitute a putative type IV secretion system believed to be acquired horizontally. Two of these virulence factors potentially interacted with the human immune system under in vitro conditions and appear to be involved in Helicobacter persistence. Most persistent microbes seemingly evolve strategies to foil host responses and gain a niche. However, it seems that there is fine tuning between microbial immune evasion and maintenance of the growth fitness. For example, H. pylori both downregulates T-cell responses through the VacA mediated cell cycle arrest, and upregulates mucosal proinflammatory pathways by CagA. Surprisingly in our studies, the proteins (above) appear to be able to perform both the immune stimulatory and immune evasion tasks single handedly (unpublished). Chronological evolution: As a part of our ongoing studies on molecular epidemiology of H. pylori in different patient populations, we have used a set of serial isolates as a model of chronological evolution. These were obtained from different niches of the stomach of an individual spanning periods as long as 10 Years. These isolates have been profiled using whole genome microarrays and pan-island sequencing; parts of the pathogenicity islands have been found to rearrange over time. Interestingly these rearrangements do not bring change in pathological severity of the disease meaning that interplay of several unknown virulence factors is possible (Prouzet-Mauleon et al., 2005. J Clin Microbiol 43:4237-4241 and Alvi et al., 2007. J Clin Microbiol. 45:4039-4043). Studies using whole genome sequence of these isolates using Solexa-Illumina sequencing platforms are planned. Infectious triggers in Type-1 diabetes: The role of pathogenic mycobacteria in diabetes has been a focus of speculation since a decade without any meaningful insights into the mechanism of diabetes causation vis a vis mycobacterial factors. M. avium subsp. paratuberculosis (MAP) is a zoonotic pathogen whose association with autoimmune diseases such as Crohn's disease in humans is now established. The objective of our study in this case was to investigate any association of MAP with other chronic diseases such as type 1 diabetes mellitus (T1DM), where the involvement of a persistent pathogen such as MAP could be the trigger. For this purpose, 59 diabetic patients and 59 healthy controls reporting at the diabetology service of the University of Sassari, Italy were investigated for the presence of antibodies against two recombinant proteins of MAP and the whole-cell lysate. Extremely significant humoral immune responses to recombinant heparin binding hemagglutinin and glycosyl transferase proteins and the whole-cell lysates of MAP bacilli were observed in T1DM patients and compared to those of healthy controls (Sechi et al., 2008, Clin Vaccine Immunol. 15:320-326). Presence of MAP in the blood of T1DM patients was also confirmed by a PCR method based on IS900 element in the genome of MAP (Sechi et al., 2008a, Clin Infect Dis. 46:148-149). Also, we further confirmed these observations by the use of a phage based ELISA method that identified live, circulating MAP bacilli through the detection of a cell envelope protein mptD by specific M13 phage, fMptD. Our results demonstrated fMptD ELISA assay to be highly accurate and sensitive to detect MAP bacilli in a large fraction of T1DM patients as compared to non-diabetic controls (Rosu et al., PLoS ONE, 2009). We found no obvious association of MAP with the incidence of T2DM in Sardinian patients (Rosu et al., 2008, Ann Clin Microbiol Antimicrobials 7:9). Finding evidence of MAP involvement in T1DM is an important finding that might serve as a foundation stone in establishing an infectious etiology for T1DM. Rapid identification of infectious agent such as MAP in diabetic patients at the level of clinics might be helpful in deciding timely initiation of therapeutic interventions, such as the insulin administration. Last updated: May 21, 2009 |
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| Pathogen Biology Laboratory School of Life Sciences, University of Hyderabad, India [http://www.pathogen-evolution.org] |
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Pathogen Biology Program - Extended Group |
| Poverty alleviation through infection control - science in this lab stregthens the millennium vision of Dr A P J Abdul Kalam, former President - make India one of the world's first five economic powers in 2020 |

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Key publications from our extended group |
| The PLoS ONE Prokaryotic Genome Collection |

| Strain specific virulence factors from plasticity region cluster of H. pylori participate in proinflammatory and apoptotic activities - one such protein displaying a PAS fold |
| Voices of Open Access! |