Entry for:2019 Queensland Women in STEM Prize
1. Project summary (maximum 150 words)
Cancer, a chronic disease has a significant impact on national health. A number of drugs have increased the survival rates of patients with cancer. However, these drugs wipe out healthy cells along with the cancerous ones, which affects the well-being of the patients. In order for the drugs to be effective and safe, drug designers should know both the structure of the drug; in my case carbohydrates called glycosaminoglycans (GAGs) and the structural elements of the specific target proteins. My research focuses on development and application of advanced computational techniques for understanding the fine structure and interactions of GAGs with proteins that are implicated in cancer. This computational framework for carbohydrate-protein interactions offers a faster and economical approach for the generation of polysaccharide-based therapeutics not only for cancer but also for other infectious diseases. My work will also open new avenues for the field of informatics for carbohydrates within Australia.
2. How does your project benefit Queensland? (maximum 500 words)
Healthcare systems in developed countries like Australia are struggling to cope with chronic diseases like cancer and asthma. According to cancer council, nearly 27,000 Queenslanders are diagnosed with cancer each year and over 8,700 Queenslanders will die of the disease, and around 11.9% Queenslanders have asthma. People with chronic conditions are more likely to report a poor quality of life. It is therefore important we develop and test interventions that are effective, clinically feasible and sustainable in more difficult economic times. To address this, Australian researchers (Griffith University, Curtin University, University of Queensland and the University of Melbourne) are developing novel drugs based on negatively charged carbohydrates called glycosaminoglycans (GAGs) to target chronic and infectious diseases.
GAGs often adorn the cell surface of the cells and play critical roles in a large number of biological processes in cancer biology, immune response, inflammation, and pathogen invasion. Understanding the chemistry and biology of GAGs is hard despite their chemical similarity with DNA owing to the negative charge and numerous potential configurations. Major technological advances are necessary to decode GAG structure - function relationships to enable the design of therapeutics for modulation of biological processes. My research addresses this key issue by focusing on basic science and computer modelling to explore structure and interaction of GAGs with key proteins and this in turn will accelerate optimisation of GAG analogues with increased potency and binding selectivity towards specific proteins involved in disease manifestations. It is expected that computer models will help to cut time off the drug discovery timeline. The aim of this research is drug design and development of new therapeutic molecules within next 2-3 years through collaboration with chemists and biologists in Queensland. The ultimate goal is to test these designed molecules for toxicity and to cancer patients in future.
GAGs play an important role as coating materials for implants, components of 3D‐constructs such as tissue engineering scaffolds and hydrogels. The comprehensive and coordinated development of tools to analyse protein-GAG interactions will also benefit the additive manufacturing/material science industry in Queensland. I am collaborating with A/Prof Travis Klein (QUT) to understand the biophysics of hydrogels using advanced computational methods.
Queensland government together with Griffith University has invested heavily to build the Institute of Glycomics to proactively participate in pharmaceutical development and realize the full potential of carbohydrate drugs for patients in Queensland. I am collaborating with leading glycoscience research group of Prof. Vito Ferro (University of Queensland;UQ) and his collaborators at the Institute of Glycomics and UQ leading to more advances in healthcare, providing prolonged benefits for Queensland into the future. This collaboration will provide exceptional opportunities for the training of PhD students, an exceptional contribution to the Queensland’s knowledge based economy. Through research, technologies and skilled staff and students, this project will further strengthen Queensland as a global innovation hub. My research in this direction directly aligns with the Queensland biomedical roadmap focusing on human health and informatics.
3. What STEM promotion/engagement activities do you do/have you done? (maximum 500 words)
I have a Bachelor’s degree in computer engineering and postgraduate degrees in life sciences. I am currently a research fellow in computational chemistry in the school of Mathematical Sciences, QUT. This field gained significant recognition when Walter Kohn and John Pople won the Nobel Prize in Chemistry in 1998 followed by Martin Karplus, Michael Levitt, and Arieh Warshel were awarded the 2013 Nobel Prize in Chemistry. Unlike computer science and medicinal chemistry, gender issues in this field are less rife today than 40 years ago due to efforts like FemEx, a project funded by the Norwegian Centre for Theoretical and Computational Chemistry (CTCC) and the Research Council of Norway. Women in many parts of the world were able to lead in both academic and research in this field, as can be seen in http://iopenshell.usc.edu/wtc/. Along these lines, I have continued to represent women by participating in both national and international conferences such as the 1st Zing conference in computational chemistry, Biophysics and Proteoglycan conferences. I am also an active participant of the Association of Molecular Modellers of Australasia, a forum for computational chemist and molecular modellers in Australia and Asia Pacific.
The highlight of my career is the fact that I am able to apply my training in computing and work experience with a pharmaceutical company to solve complex problems in areas such as chemistry, biology and material science. It is a privilege to be able to share my knowledge with my female students. For instance, I had the opportunity to supervise two High school girls under the Sanofi-Aventis BioGENEius Challenge of Western Australia. They were among the few students to make it to the top ten in the competition. I have also supervised one Honors and one Masters student at Curtin University on projects in this field. Moreover, my first PhD graduate successfully transitioned from mechanical engineering to computational chemistry. She continued my tradition to receive commendation by the examiners for a PhD thesis by publication. Understanding her potential, curiosity and passion for translational research, I have encouraged her to pursue postdoctoral research at the Translational Research Institute under my mentorship and also under Prof. Derek Richard’s supervision. As an emerging leader in computational chemistry & biology, I’m actively working on inspiring girls to take up a research degree within QUT. In this perspective, I have recently started supervising a female PhD candidate. As part of the Work Integrated Learning program this year at QUT, I will have opportunity to supervise undergraduate students on a short 6 weeks project and promote how science and math benefits them every day. I actively participate in events like Tertiary Studies Expo (TSXPO) and guest lectures and encourage students to spend a day with our group to give them practical knowledge and understanding of the impact that they can have being part of innovative projects.
Dr Gandhi is a trained computer engineer and worked as Department-in-charge (Bioinformatics and modelling) at the Zydus Research Centre, a multinational pharmaceutical company in India. She did her...