Molecular Immunology and Microbiology

About Us

The department is actively pursuing the following research programs

List of Projects:

(1) Characterization of AMPs isolated from Rabbit vaginal fluid and their role in vaginal Innate Immunity (Partly funded by International Partnership on Microbicides, & ICMR intramural grants)

Several antimicrobial peptides (AMPs) have been identified by our group from diverse natural sources and have undergone pre-clinical evaluation for use as safe and effective anti-HIV molecules. One of the haemoglobin derived peptide (HbAHP-25) designed by an in silico approach appears to be promising as an anti-HIV peptide.

(2) Expression of hemoglobin-α and β subunits in human vaginal epithelial cells and their functional significance (ICMR intramural grants)

Hemoglobin (Hb) is a major protein involved in transport of oxygen. It consists of Hb-α and Hb-β subunits, which are normally expressed by cells of erythroid lineage. However, till recently, it was not known whether non-erythroid cells like vaginal cells synthesize Hb and whether it has any functional significance. Our study revealed that Hb-α and Hb-β are expressed at both mRNA and protein level in human primary vaginal epithelial cells. This expression was significantly upregulated following LPS and H₂O₂ treatment. We also detected the binding sites for LPS and/or H₂O₂ activated transcription factors on Hb promoter in vaginal epithelial cells.

 (3) Human vaginal epithelial cells augment autophagy marker genes in response to Candida albicans infection (funded by DBT-ICMR)

Autophagy plays an important role in clearance of intracellular pathogens. However, no information is available on its involvement in vaginal infections such as vulvo-vaginal candidiasis (VVC). VVC is intimately associated with the immune status of the human vaginal epithelial cells (VECs). The objective of our study is to decipher the role of autophagy during Candida albicans infection of VECs. We are currently studying this in-vitro using vaginal epithelial cell line VK2/E6E7 (Fig. 1) and in-vivo using mice having a conditional knockout of autophagy related gene in the progesterone receptor expressing cells.

 (4) Studies on the Modulation of Vaginal Immunity during Host-Pathogen Interactions in Response to Microbicide (Partly Funded by ICMR intramural grant)

In endocervical epithelial cells (End1/E6E7) miRNA, let-7f plays a key regulator in mediating TLR tolerance. However, the underlying molecular mechanism for let-7f regulation in human endocervical cells remains largely unclear. To identify the targets of let-7f, we performed microarray after knocking down of let-7f, and identified several differentially regulated transcription factors. C/EBPa, C/EBPβ, Blimp-1 and NFATc1 were differentially regulated. Of these, C/EBPβ was found to have binding sites in the let-7f-1 promoter. Knockdown and overexpression studies were carried out to validate the effect of C/EBPβ on let-7f expression. Chromatin immunoprecipitation (ChIP) assay was performed to corroborate the findings. Knockdown of C/EBPβ results in repression of let-7f expression and over expression of C/EBPβ increases let-7f expression. In conclusion, let-7f-1 is a direct target of transcription factor, C/EBPβ.

People

Department Email Id: immunol@nirrh.res.in

Projects

• Characterization of AMPs isolated from Rabbit vaginal fluid and their role in vaginal Innate Immunity (PI: Dr. K V R Reddy) (Funded By IPM/ICMR)
• Expression of haemoglobin-α and β subunits in human vaginal epithelial cells and their functional significance (PI: Dr. K V R Reddy)  (Funded By ICMR)
• Human vaginal epithelial cells augment autophagy marker genes in response to Candida albicans infection (PI: Dr. K V R Reddy) (Funded by DBT/ICMR)
• Studies on the Modulation of vaginal immunity during host-pathogen interaction  in response to microbicide (PI: Dr. K V R Reddy) (Funded by ICMR)
• Approaches for prevention of Biofilm formation by Gardnerella vaginalis (PI: Dr V Bhor) (Partly funded by DBT- Rapid Grant for Young Investigators Programme)
• Studies on HIV-1 gp120 Mediated α₄β₇Integrin Dependent Signaling in T Cells and its Role in HIV-1 Pathogenesis. (PI: Dr V Bhor) (Partly funded by DBT-ICMR)
• Development of a multistrain probiotic Lactobacillus formulation effective against reproductive tract infections (PI: Dr Clara Aranha)

Completed Projects:

• Endometrial functional markers to evaluate implantation defects in human endometrium (Funded by ICMR)
• Establishment of Non-Human Primate Facility for reproductive health research (Funded by DST)
• Development and preclinical evaluation of naturally occurring antimicrobial peptide, magainin for the prevention of STIs/HIV including unplanned pregnancies (Funded by ICMR)
• Strengthening of research programs to realize therapeutic potential of embryonic stem cells (Funded by MHFW)
• In vitro evaluation of peptide based microbicides for anti-viral activity (Funded by DBT-ICMR)
• Identification and characterization of cationic polypeptides with antimicrobial properties from rabbit epididymis (Funded by DBT-ICMR)
• Design of germ cell specific transgene constructs to investigate early events in spermatogenesis (Funded by DST)
• Functional Significance of Transcription Regulatory Factor Oct-4 in the Early Events of Spermatogenesis in Mice (Funded by Indo (DBT)-German)
• Nisin: The antimicrobial peptide for the prevention of sexually transmitted infections including HIV/AIDS (Funded by ICMR)
• Identification and characterization of Putative Cis-Regulatory Elements (CREs) of the mouse c-kit promoter and their role in spermatogenesis (Funded by DST/ICMR)
• Isolation of pathogens associated with STIs and testing against selected microbicide in vitro (Funded by DBT-NE)
• In-silico design of peptide(s) having anti-HIV activities and pre-clinical evaluation (Funded by ICMR)