Research Intern (TCOS fellowship duration: 1 April 2015 to 31 July 2015)
Will be studying B.Sc (H) Microbiology at Bhaskaracharya College of Applied Sciences, Dwarka
CBSE Class 12 (Physics, Chemistry, Biology and Mathematics) from Delhi Public School,
R. K. Puram. Best of four aggregate = 92%
‘Beware of Greeks Bearing Gifts’: Exploiting the Glucose Avidity of Tumour Stroma to Deliver Metabolic Inhibitors via Trojan Horse Nanocapsules’
Original thesis nominated for the Young Mind Award @ BioAsia 2015: The Global Biobusiness Forum, organized by the Federation of Asian Biotech Associations, Hyderabad on behalf of Government of Andhra Pradesh with the support of the Government of India.
Most tumours grow as solid masses of tissue and comprise of two distinct but interdependent compartments: the neoplastic cancerous cells and the stroma. Recent investigations suggest that the ‘glycolytic’ stromal fibroblasts are metabolically coupled with the ‘oxidative’ neoplastic cells, and that the cancer cells use hydrogen peroxide as a weapon of oxidative stress to enslave normal fibroblasts by causing DNA damage, inducing autophagy and mitophagy. The stabilisation of HIF-1 leads to a primarily upregulated glycolytic phenotype. The activation of NFkB results in an inflammatory response such that these transformed fibroblasts also begin to secrete hydrogen peroxide, further ‘fertilising’ the tumour microenvironment. I propose the use of glucose as a decoy to gain entry into a malignant, glucose avid cell, to deliver metabolic inhibitors inside it. The glucose avidity gives a biochemical basis to prefentially target cancerous tissue, as utilised in positron emission tomography. Also, 2-deoxy-α-D-glucose (2-DG) polymer is used to construct the membranes of the nanocapsules. 2-DG is an inhibitor of glucose metabolism, but is actively taken up by the cell, and hence can be used to against sensitised cells which are predominantly glycolytic. Since nanocapsules deliver a higher concentration of pharmaceutical agent to a desired location, they provide targeted and efficient therapy, and can effectively overcome dose-limiting factors. In vivo, these Trojan Horse nanocapsules could be locally administered in conjunction with anti-oxidant therapy following the embolisation of the blood vessels supplying the tumour.
dPABBs: A Novel in silico Approach for Predicting and Designing Anti-biofilm Peptides
Manuscript under consideration. Accepted for a Poster Presentation at the at the Drug Discovery and Therapy World Congress 2015 to be held in July in Boston, USA.
Biofilms are increasingly being recognised for their causative role in persistent infections and nosocomial diseases. This adaptation represents an important multicellular strategy used by bacteria to evade the host’s immunity and become highly resistant to conventional antibiotics. Given the clinical relevance of biofilms, it is imperative that alternative therapeutics are proactively sought. We have developed dPABBs, a webserver that facilitates the prediction and design of anti-biofilm peptides. Exploiting the intimate connection between quorum sensing and biofilms, we have built four SVM and Weka models (using 80 antimicrobial peptides with anti-biofilm activity as the positive dataset and 88 quorum sensing peptides as the negative dataset) which were observed to discriminate peptides on the basis of their amino acid composition (maximum accuracy, sensitivity, specificity and MCC of 95.24%, 92.50%, 97.73% and 0.91, respectively, on the training datasets). dPABBs utilises a combined evidence strategy involving simultaneous predictions from multiple models for the prioritisation of putative peptides with greater confidence, while its mutant generation feature allows the design of peptides with improved activity. Positive predictions were also obtained for 11 FDA-approved peptide drugs and nine antimicrobial peptides in clinical development, indicating at their possible repurposing for anti-biofilm therapy. dPABBs is freely accessible on: http://ab-openlab.csir.res.in/abp/antibiofilm/.
Mitochondrial diseases: genotype to phenotype correlations to understand the heterogeneity in disease manifestation
Role of bacterial membrane vesicles containing Mtb molecules (lipoglycans and lipoproteins) in host-pathogen interactions
- Senior Diploma in Kathak Dance from Prayag Sangeet Samiti, Allahabad.
- First prize in story writing and narration at ‘Parampara-2012’, an international inter-school competition at Delhi Private School, Sharjah.
- Was a member of the Indian delegation to the 11th International Children Festival at Crimea, Ukraine, which was organized by All-Ukrainian charitable Foundation of Hope and Good, the International children center “Artek”, the Ministry of Social Policy of Ukraine and the Ministry of Foreign Affairs of Ukraine under the aegis of the Cabinet Ministers of Ukraine, and was attended by representatives of 54 world countries. Represented India at the 3rd session of the General Assembly of the International Children’s League of Nations (ICLN), an international public organisation within the framework of the festival, and was appointed the regional coordinator of the project “Me and the Environment”. Was among the signatories of the Appeal addressed to the Leaders of States, International Organisations and adults of the world in general, enlisting the resolutions adopted by the General Assembly of the ICLN at its closing ceremony on 1 August 2012. Also awarded a diploma for creative achievements in phytodesign.
- Finished in the top 5 of the ‘Flag for the Future’, a global contest to design a flag representing the youth of the world; a flag for peace, hope and global community, organized by Greenpeace International in collaboration with the World Association of Girl Guides and Girl Scouts. The flag design was displayed at the North Pole in April 2013 as a capsule containing the signatures of almost 3 million Arctic defenders was planted at the sea-bed. Became an activist with Greenpeace India. Represented the ICLN and Greenpeace at a television programme called ‘Right to be Heard’, broadcasted on Headlines Today, a national news channel. Posed questions to the Minister of Environment and Forests, Ms. Jayanti Natrajan and submitted the ICLN Appeal to her.
- Participated in the discussion on the relevance of the ‘Swachh Bharat Abhiyaan’ (Clean Indian Campaign) on NDTV India: http://khabar.ndtv.com/video/show/badi-khabar/badi-khabar-swachh-bharat-swachh-vidyalaya-340305?q=/video/show/badi-khabar/340305
- Participated (audience member) in the panel discussion on India’s Mars Mission (Mangalyaan) on NDTV 24×7: https://www.youtube.com/watch?v=zQh5iv4nHXM&feature=youtu.be