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​Doctorate thesis​

Systems biology of breast cancer

(VIVA examination successfully completed on 25th September 2013 at Nottingham Trent University, UK)
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The entire research was focused on identifying oestrogen receptor (ER)-associated genes, inferencing gene-gene interactions and implementing a non-reductional systems biology approach using Artificial Neural Networks (ANNs) predictive modelling method on high throughput breast cancer microarray datasets. To achieve this, a multilayer perceptron model coupled with a backpropagation algorithm and Monte Carlo Cross-Validation strategy was applied.

 

The predictive performance of ANN to predict ER status in samples was assessed using Receiver Operating Characteristic curves and measurement of sensitivity, specificity and accuracy in multiple independent runs and repeats to investigate the consistency of performance. Promisingly, the ESR1 gene (coding for ER-alpha subunit) was found to be the best predictor for ER status by ANN along with other breast cancer-related genes such as GATA3, FOXA1, CA12 etc. at the higher rank order. ANN-based network inferencing method identified ER status-specific interaction hubs. One of these, DACH1 expression was validated and found to be highly associated with clinicopathological and breast cancer-specific markers studied in clinical samples. Furthermore, DACH1 was also found to be an independent prognostic indicator for breast cancer-specific survival when hormonal treatment was considered.

 

As the novelty;

 

(i) To investigate cross-talk between ER components, ER-alpha (ESR1) and ER-beta (ESR2), respective interactomes were created using the ANN-based network inferencing method. Furthermore, to model ER pathway, the known interactors of both ESR1 and ESR2 were modelled using in-silico interaction databases. The simulation of ER pathway revealed a close association between ESR1, PGR, AR, RARA, FOXA1, EGFR and XBP1 which were biologically relevant.

 

(ii) A non-reductionist or additive approach for ER system was implemented, wherein two levels of serial addition of predictive markers were achieved. Later this approach was extended to PGR and HER2 systems. Cumulating ER, PGR and HER2 systems to represent systems biology of breast cancer successfully identified biological relevant entities and linked genes between systems. Furthermore, some important cross-talk were validated using known interaction databases.

Post-Graduate dissertation

In Vitro 60Co Dose-Response Curve for Biological Dosimetry derived from Single Cell Gel Electrophoresis (COMET ASSAY)

Submitted to Dept. of Human Genetics, Sri Ramachandra University,  India (2006)


​To quantitatively estimate the stochastic DNA damage in patients undergoing radiotherapy, the single cell gel electrophoresis (COMET assay) was used as a biological dosimetry; various dosage of radiation was considered to develop a standard curve. Total of 50 comets under each dose were analyzed which showed considerable decrease in head length and increase in tail length as the dose increased, and a linear regression curve for head length (R2=0.8479), tail length (R2=0.9615) and tail/head ratio (R2=0.9257) was obtained. In general, the comet assay is considered as a suitable and a rapid test for DNA-damaging potentials in biodosimetric studies.

Under-Graduate dissertation

Isolation of Antibiotics from Soil
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Undertaken for the partial fulfilment of Bachelor’s Degree in Biotechnology from SSMRV Degree College, Bengaluru, India (2004)


​Soil acts as a vital source of nutrients for growing plants. It is also composed of antibiotics which give protection during the development stages. In an attempt to isolate these antibiotics from the soil, we collected soil samples from various places in Bangalore city, India. To develop cultures of microorganisms growing presence in the soil, we serially diluted soil solution and cultures. The colonies that developed ion agar plates were counted and the growth rate was measured. The antibiotics were from broth culture and simultaneously the colonies were characterized for their identification. The Actinomycetes and Streptomycetes colonies were characterized and antibiotics were isolated and purified by the activated charcoal method. The reactivity of the antibiotics was tested against the commercially available grades of antibiotics. As a result, we were able to isolate and characterize microbial colonies from the soil. The reactivity of purified and isolated antibiotics were equivalent to commercially available antibiotics. This was an in-house developed project for the partial fulfilment of a bachelor's degree.



(Image courtesy: Vinod Kumar S) 

Technical reports

​Polyclonal antibody production in rabbits
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Submitted to Dept. of Human Genetics, Sri Ramachandra University, India (2006)


​Aiming to produce polyclonal antibodies against Human IgG, Human IgG was isolated and injected into rabbits with an appropriate adjuvant system. A specific protocol of 60 days with primary immunization and booster immunization doses was carried out with successful bleeding procedures. At every bleed, the quantity and quality of the antibody produced was monitored. A detailed protocol and report was submitted to the corresponding department.

Practical training in Molecular Biology

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On-Job training report submitted towards the partial fulfilment of Under-Graduate degree



Completed at Jain Institute of Vocational and Advanced Studies (JIVAS), Bengaluru, India (2004)​



The training program focused primarily on hands on training in molecular biology experiments such as DNA extraction, isolation, restriction digestion and ligation from both Plasmid and genomic sources. The training was also extended to RNA isolation from genomic source. The training also helped me to develop confidence in handling various laboratory instruments and machines.



(Image courtesy: Vinod Kumar S)

Summer Training in Diagnostics

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Completed in Medinova Diagnostic Centre, Bengaluru, India.​

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​The training included various diagnostic tests in the fields of medical biochemistry, haematology, pathology, radiology and microbiology. The training was my first exposure to medical biotechnology. Medinova Diagnostic Centre, being a successful and established medical service, encouraged and exposed me to move forward in biotechnology.

 

 

 

 

 

 

 

 

 

 

 

 

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