Blue Peter Research Centre (BPRC)

Immunology, Molecular Biology & Biochemistry Division

Immunology & Molecular Biology Team
1.
Dr. Vijaya lakshmi V, M.Sc, Ph.D Group Leader
2.
Prof Indira Nath, MD, FRC Path, DSc (hc Paris 6), FNA, FNASc, FASc, FAMS, FTWAS, Director
3.
Dr Sarita Ranjan, PhD, DST Young Scientist
4.
Ms. Mehervani Chaduvula, M.Sc, Lab Technician
5. Ms. Vidyagouri Shinde, M.Sc, Ph.D Student
6 Ms. B. Anuradha, M.Sc, Ph.D Student
7 Ms. R. S. Sharada, M.Sc, Ph.D Student
8 Ms. K. Sudeshna, M.Sc, Ph.D Student
9 Mr. Md. Ahmed, Lab Attender
   
  Bio-Chemistry
1 Prof. M. P. J. S. Anandaraj, PhD, Consultant
2 Mr. Venkat Karunakar, M.Sc, Ph.D Scholar
   

Areas of research interest

The main goals of this laboratory are to understand different aspects of the causes of certain infectious diseases such as leprosy, tuberculosis (TB) and HIV-tuberculosis co-infection. Whether an individual infected with the bacteria (leprosy, TB) or virus (HIV) develops active disease or not depends to a large extent on his or her genetic make-up. Several genes are responsible in either conferring protection to individuals or in rendering them susceptible. Knowing what these genes are and detecting their presence in individuals may help in understanding the mechanisms involved in the disease process and this may lead to developing strategies either to prevent a disease by way of vaccinations or perhaps cure the patient by way of treatment.

Immunity: Out of the nearly two billion people infected with M. tuberculosis only eight to nine million may develop disease annually. Hence, the immune response stimulated during infection is highly efficacious in the vast majority of infected individuals. However, control of infection is incomplete and the bacteria are not eradicated, so that the risk of reactivation, even decades after infection, remains. It is the balance between the host’s defences and the persisting bacteria that eventually decides the clinical outcome of the disease. One of the goals of this division is to understand the factors that influence this balance. The induction of interferon-gamma (IFN-y) secretion by T cells has been shown to be critical for protection against tuberculosis. The levels of this and other related cytokines are correlated to the clinical status of the individuals.

Genetics: The host defences are influenced by the genetic make-up of the individual. Evidence from studies of twins with leprosy or TB, and of family clustering of cases suggests that some factor(s) which is (are) inherited influence(s) susceptibility to the disease. Studies concerning the genes that might influence susceptibility to Mycobacterium leprae (leprosy), Mycobacterium tuberculosis (TB) and human immunodeficiency virus (HIV) have resulted in the identification of several genes. There is a need to study the influence of these genes in the local populations. Such studies are undertaken in this laboratory. For example, genes which encode for proteins involved in immune responses like IFN-y and Interleukin-10 are studied in patients with leprosy, TB and/or HIV-TB. A project on the study of toll like receptors (TLR-2) and P2X7 (macrophage markers) genotypes in tuberculosis is presently being funded by the Department of Biotechnology.

Vaccination: BCG vaccine has been in use for protection against TB and leprosy for almost a hundred years now. In India, BCG vaccine is administered only once soon after birth to immunise the child life-long. However, the vaccine is not hundred percent effective as evident from the immunological studies conducted by us in a large number of children and the reported incidence of tuberculosis which continues to rise. Our studies also indicated that the immunity conferred by the vaccine wanes with age and the effect does not seem to last for more than four to six years and it is around this age that the incidence of TB rises as illustrated in the graph. There is therefore a dire need to boost the effect of the vaccine and to maintain the immunity of the child. But before this the exact immune response elicited by BCG vaccination and its mechanism of action within the host need to be elucidated.

Studies of the immunological events that occur within the human host after BCG vaccination are almost totally lacking and are warranted. We have identified a protein (BCG-Ag85A) present in the supernatants of BCG when cultured in liquid media. BCG-Ag85A is secreted by the bacteria and is present in abundance in the cultures. It could be demonstrated by us that the BCG-Ag85A is highly immunogenic and hence may be a promising booster-vaccine candidate as it sensitizes the immune system for strong T-cell proliferative responses and IFN- production in children vaccinated with BCG. Further studies in a larger number of children are underway.


Main
Aims:

To identify the relevant genes and their influence on the immunity of an individual to leprosy, tuberculosis and/or TB-HIV co-infection
To work towards developing a booster-vaccine for tuberculosis using BCG-Ag85A
To be able to detect live bacteria causing leprosy, in environmental samples such as soil and water by the use of sensitive molecular tools
To conduct epidemiology studies by typing the strains of bacilli causing leprosy using molecular tools. The chains of transmission could be probably be identified by tracking the clinical isolates using these tools
To study the immunological reactions and nerve function impairment (NFI), leading to most of the deformities and disabilities seen in leprosy. The study is a multi-centre project involving national and international organisations.

Collaborative research projects

The laboratory has both national and international collaborative research projects. Centre for DNA fingerprinting and Diagnostics (CDFD), Department of Genetics, Osmania University, Institute of Genetics and Hospital for Genetic Diseases and Mahavir hospital are involved in the national studies and Colorado State University, USA and London School of Hygiene & Tropical Medicine in the international studies. A multi-centric project on the study of viability of M. leprae bacteria in clinical samples and possibility of its presence in the environment using nucleic acid amplification techniques, funded by ICMR and molecular epidemiological studies on leprosy are presently being conducted.

With an aim to study the secondary complications of the leprosy resulting in most of the deformities and disabilities seen, the INFIR Cohort Study, a multi-centre project involving national and international organisations, was set up. For identifying the chains of transmission, another project IDEAL (Initiative for Diagnostic and Epidemiological Assays for leprosy) was formulated as a collaboration between Blue Peter Research Centre, Colorado state university and London School of Hygiene & Tropical Medicine.


Facilities & techniques


The department has a Molecular Biology Laboratory with pre- and post-PCR facilities which allows visualization of DNA (the basic unit of genes) by amplifying it several times. In the Immunology Laboratory facilities are available for assessing the immunity of individuals by culturing the immune cells and detecting the chemical mediators (cytokines like interferons/interleukins) released by them. The division also has a walk-in cold room.
VNTR of M.leprae

 

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