Several early-career scientists submitted research proposals as part of AstraZeneca’s R&D Postdoctoral Challenge in March 2022 to accelerate drug discovery across some of the world’s most challenging medical concerns.
Among the six winners from Africa, Middle East and Europe was UAE-based researcher, Dr. Rakhee K. Ramakrishnan, who is a Postdoctoral Research Associate at the Research Institute for Medical and Health Sciences at the University of Sharjah. Her research on microbiome-based therapeutics demonstrated a substantial impact on patients and healthcare systems.
As a result, she received a fully supported postdoctoral research position with access to AstraZeneca’s knowledge, compounds, novel tools and technologies, as well as mentorship support. In addition, she was given the opportunity to pursue fully funded, two-year research positions in one of AstraZeneca’s strategically located R&D facilities in Cambridge (UK), Gaithersburg (US), and Gothenburg (Sweden).
Excerpts from an interview with Dr. Ramakrishnan:
Please elaborate on your proposal on a multi-OMICS approach to analyse the airway microbiome and associated metabolome in asthma.
There has been a growing interest in microbiome research spread across various parts of the body. I am particularly interested in the airway microbiome and how it is increasingly associated with overall lung health.
Many studies have demonstrated that the airway microbiome is home to diverse microbial communities and suggest a distinct airway microbiome in those with chronic respiratory diseases. The complex bacterial communities in our lungs have an important function to promote and maintain a state of immune tolerance, preventing undesirable inflammatory response caused by inhalation of environmental stimuli.
Airway dysbiosis is characterised by an altered composition of the airway microbiome and every study to date has shown a clear aberration in microbial composition and diversity in asthmatic airways compared to healthy subjects. While this dictates many aspects of asthma, it needs to be understood further on a molecular level.
My research interest is centred on the role of mitochondria – known as the ‘powerhouse of the cell’ – and how its dysfunction can lead to a diseased state. My focus is on better characterising the metabolic interaction between the airway microbiome and host in asthma and proving that airway dysbiosis predisposes the airway cells to mitochondrial dysfunction due to a dysregulation in the microbial metabolite profile.
To do so, a multi-OMICS approach is notable due to its ability as a research tool to uncover meaningful messages from the wealth of biological and sequencing data available from multiple “omes” – such as the microbiome transcriptome and metabolome among several others. This tool has immense potential in developing a comprehensive understanding of the mitochondrial changes that occur during asthma development, bringing us a step closer to potentially unlocking a new way to treat asthma patients.
Tell us about the significance of winning the AstraZeneca R&D Postdoctoral Challenge, especially in your area of research.
These initiatives are incredible for early career researchers, as it gives us the opportunity to challenge ourselves and develop innovative research ideas. More importantly, it helps us potentially transform the way certain overlooked diseases are treated and translate these ideas into improved outcomes for patients.
Asthma is a particularly complex and sometimes overlooked disease that has interested me for a while, which is why I appreciate the platform that the R&D Postdoctoral Challenge provided me.
COVID-19 offered a significant lesson for us on the immense potential of collaboration. When we fight on a united front, as we did at the height of the pandemic, we can achieve rapid breakthroughs in science to the benefit of people in most need of care.
Dr. Rakhee K. Ramakrishnan
Mitochondrial metabolism and airway dysbiosis are niche topics. How does mitochondrial metabolism, together with autophagy, regulate stress responses?
Mitochondria sit at the heart of my research and speciality. They not only sense cellular insults such as allergens, infection, and inflammation among other aberrations, but also have the potential to respond quickly to these challenges. While asthma is not conventionally seen as a mitochondrial disease, mitochondrial dysfunction is known to drive various disease features specific to asthma. This is what triggered my interest in taking a closer look at the mitochondria in airway structural cells to understand how their dysregulation drives subepithelial fibrosis in asthma during my PhD at the University of Sharjah.
Considering the complexity of the airway microbiome, which represents not just one microbial community but an entire ecosystem, I have a great appreciation for multi-OMICS as a research tool as it simultaneously integrates data from different omics to offer a more comprehensive view. A condition like asthma involving several complex interactions requires a certain level of resolution for proper examination. Multi-OMICS is a rather powerful research tool at our disposal to serve this end.
This article appears in the latest issue of Omnia Health Magazine. Read the full issue online today.