Drug development, from basic research to market entry, sometimes takes 10 – 15 years, a testament to the immense complexity of the entire R&D process. Some drugs dont even make it due to regulatory hurdles. It is very rare to interview a scientist who has been through multiple stages of drug development.
Our next pathbreaker, Anita Patil, completed fundamental research on Protein Characterisation, went on to do her PostDoc on Alzheimer’s disease and subsequently worked on the regulatory approval of a Recombinant Insulin drug.
Anita talks to Shyam Krishnamurthy from The Interview Portal about her journey from researching the building blocks of life all the way to understanding the pathways in making a new drug molecule
A great read for students interested in Life Sciences, a domain in which bioinformatics, gene therapy and cell therapy will be playing a major role in the future.
Anita, tell us about your initial years
My father worked as Farm Machinery specialist in Central Govt and mother is a house maker. I grew up in New Delhi until my post graduation. I was interested in arts and music and was overall an average student in Science. I wanted to study Medicine after school.
What did you study?
I studied B.Sc. (Honors) Zoology (Kirori Mal College at North campus, University of Delhi). We learnt from extremely knowledgeable and talented faculty. I enrolled in M.Sc. Microbiology course at University of Delhi, South Campus.
How did you end up in such an offbeat, unconventional and fascinating career?
We had several bright people teaching us, including Prof. B.K. Bachhawat (Biochemistry), Prof. A.K. Tyagi (Recombinant DNA Technology), Prof. T. Satyanarayana (Industrial Microbiology), Prof. J.S. Virdi (Immunology), Prof. O. Vijayan (Virology) and Prof. S. Srivatastava (Genetics). Prof. U. Kenkre from Tata Institute of Fundamental Research, took some special lectures that gave us an in-depth understanding of proteins. The atmosphere was charged with science. Many good seminars were held regularly. During M.Sc., we visited the National Chemical Laboratory, National Institute of Virology, University of Pune and Hindustan Antibiotics Ltd (HAL) at Pune during a trip. At HAL we learnt about fermenters which were used for the production of antibiotics and visited the analytical instrumentation laboratory. All these experiences influenced me in a big way.
Tell us about some of your internships and projects
In M.Sc. after Part I, I worked at the CSIR Center for Biochemicals, near University of Delhi as a summer intern. Two senior scientists, Dr. A.P. Joshi and Dr. SV Gangar used to direct the laboratory projects. I learnt to compute Biological Oxygen Demand (B.O.D.) for industrial effluent samples. BOD is used, often in wastewater-treatment plants, as an index of the degree of organic pollution in water. Adjacent labs were doing gel electrophoresis for identification of allergenic samples and I was acquainted with the research environment.
In Part II of M.Sc., I did research dissertation in Industrial Microbiology, which involved devising an entire project, including literature survey, planning and carrying out the experiments. Thermophilic (heat loving) microorganisms from samples of soil and composts were isolated (Bacteria, Fungi and Actinomycetes), numbered and saved in cold. These cultures were grown in a shake flask and their culture fluid was tested for the enzymes, amylases. These enzymes degrade starch, a complex carbohydrate into smaller units of glucose. Once the screening was over, the best three isolates were used for starch dissolution and alcohol production. The work was huge and absorbing. I learnt to experiment and document the experience.
After M.Sc. was over, I wanted to do research and applied for the position of a junior research fellow in a project on Archaebacterial Halophiles and Evolution of life at Bhabha Atomic Research Center, Mumbai. Halophilic bacteria can survive in extreme environments with high salt and their proteins have evolved to work in high salt. The unusually high salt concentrations make protein purification very difficult using column chromatography. We probed the purified protein for active site peptide isolation by radio labeling, chemical digestion and protein sequencing. I learnt Biochemistry, Bioinformatics and Microbiology in the research project. After my Ph.D thesis submission, I briefly taught at Food and Fermentation Technology department at UDCT, Mumbai. Interacting with M.tech. students in Bioprocess technology was a memorable experience there.
Your career path?
After my Ph.D. defense, I joined the Molecular Biophysics Unit at Indian Institute of Science, Bangalore. I worked on proteins named lectins which bind to carbohydrates. I initiated work on an animal lectin, a carbohydrate and calcium binding protein occuring in the endoplasmic reticulum. I was also exposed to Thermodynamics of protein ligand binding using titration calorimetry and protein unfolding using scanning calorimetry. I learnt protein structure based work (broadly classified as Biophysics) using X-ray crystallography and Mass spectroscopy. Recently Cryoelectron microscopy and NMR are increasingly being used for protein structure determination.
I wanted to do further research on protein structure and folding. So I applied for a postdoctoral fellowship in USA. Protein structure work in medicinal chemistry enables better drug design using recombinant enzyme assays with small molecule inhibitors as drug candidates for screening. Scientists in Medicinal Chemistry synthesize novel small molecules for drug candidate screening. Recombinant proteins are made by engineered bacteria critical for development of Protein structure, Biochemistry and recombinant Biotherapeutics based Biotechnology. The proteins need to be screened using a vast number of crystallization conditions for structure determination by X-ray crystallography. These are long term research attempts needing continuous funding. A couple of years later, I switched to applied research in protein misfolding that causes diseases. Alzheimers Disease (AD) results in loss of memory in old age. The two proteins believed to be involved in this disease were being studied in detail in Alzheimers laboratories. Initially I worked on the pathway involved in Alzheimers with a mammalian cell line model after transfection with green fluorescent protein tagged membrane receptors for selection. Later I studied the role of a membrane protein intracellular fragment in Transgenic mouse models of AD.
I returned to India to join a Biotherapeutics based company at Ahmedabad, Gujarat where I worked on cancer cell line proteomics for identifying outlier proteins in cancer. Then I worked on several diagnostic (Human Immunodeficiency Virus), Biotherapeutic (Granulocyte Colony Stimulating Factor) and Vaccine candidates (Human Papilloma Virus, Rabies). Recombinant proteins can be made on different platforms using bacteria, yeast, mammalian cell lines and insect cell lines as their workhorses. I learned the pathway for a biotherapeutic molecule using molecular biology, including upstream to downstream, analysis, quality control, quality assurance and regulatory processes. I learnt many new experimental designs with collaborators from a USA based Vaccine Company. After few years, I shifted to a company in Aurangabad, Maharashtra. I worked on several formulations and analytical projects for recombinant Insulin needed for abating Diabetes and Erythropoetin, responsible for production of new red blood cells in human body. I devised the entire analytical study which was needed by the regulatory agency in India for its approval for preclinical (animal toxicity) studies. This involved a big team of scientists, quality assurance and regulatory people as well as a preclinical team at Pune. I learnt about the pathway in making a new drug molecule from my friends in the Drug Discovery group,. I met several bright minds dedicated to the cause of vaccines and biotherapeutics here.
What were the challenges?
The main challenges I faced were the complexities of problems in biology, dealing with difficult mentors, and funding issues.
I believe that sincere hard work can keep you ahead in your field. Also networking and remaining updated with new fields and courses is very important.
What do you do currently?
I am currently looking for a challenging research position.
a) This involves using my experience in life sciences domain in various fields
b) Based on the experimental work in my research jobs
c) Reading, Going through research articles, writing to Contacts, Helping students
d) It is directly related to human wellbeing.
What are the benefits of your work to society?
My work relates directly and indirectly to health, medicine and biological applications for mankind.
Your advice to students?
Life science is a huge domain. In future, bioinformatics, gene therapy and cell therapy will be playing a major role. Apply for internships in Industry during summer. Have a very good foundation in Mathematics, Computer science, Physics and Chemistry. Medicine and Pharmacy are also very important subjects for work in Biotechnology. Also look into Science writing, Medical writing, Quality control, Regulatory, Biostatistics and Journalism as a career. Try to write articles in particular subjects of interest in Biology. Read autobiographical accounts of famous scientists. Attend good lectures in the University and colleges as well as on the web. Learn volunteering for disease based funding agencies and associations. Update your knowledge by reading latest articles, workshops and online courses.
Your future plans?