Dr Sunita Ramesh completed her PhD at the University of Adelaide, investigating the ‘Molecular Mechanisms of Zinc Uptake and Regulation in Cereals’. Abiotic stress in plants significantly affects development, growth and yield. Upon completion of her PhD in August 2002, Dr Ramesh took up a position as a post-doctoral researcher in the Plant Research Centre at the Waite Campus, University of Adelaide. She continued her research into improving abiotic stress tolerance in crop plants with a strong focus on the role of membrane transport proteins and associated signalling cascades. In 2015, Dr Ramesh was the lead researcher involved in identifying that gamma aminobutyric acid (GABA) – an inhibitory neurotransmitter in mammalian brains, is a stress signal in planta; and that a  family of anion channel proteins have a putative GABA binding motif.

In 2017, Dr Ramesh started teaching part time at the School of Biomedicine at the University of Adelaide, while continuing her plant focussed research. Whilst at the School of Biomedicine, Dr Ramesh started research into the roles of ion channels and transporters in cell motility in cancer, with a particularly strong focus on brain cancer. Currently Dr Ramesh’s research focuses on identifying novel natural compounds and their modes of action in limiting tumour cell movement.

Dr Ramesh joined Flinders University as a Lecturer in Molecular biology in 2020 and established Transport Physiology and Signalling research group. Her laboratory uses several heterologous expression systems such as Xenopus oocytes, E. coli, yeast, tobacco cells, plants, and cell lines to answer research questions. Her research group focusses on improving abiotic stress tolerance in crop plants and identifying novel pharmacological compounds to limit brain cancer invasiveness.

Research Program

My research program involves two major research themes – Food security and Human health.

Under Food security theme, our group investigates the role of membrane proteins and associated signalling cascades in improving crop abiotic stress tolerance. Of particular interest is the role of non-protein amino acid, gamma aminobutyric acid (GABA) in ameliorating abiotic stress and its role in plant stress signalling. The concentration of GABA increases several folds when plants are exposed to stresses such as salinity, drought, low pH, and alkaline soils and this helps cope with adverse conditions. However, the insights and molecular basis of this mechanism of action remain elusive. We focus on transporters and channels expressed in abiotic stress that may be regulated by GABA and if manipulation of these proteins can lead to improved stress tolerance.

Plant-soil-microbe interactions play a key role in development, growth, yield and plant health. These interactions are also key drivers of the ability of plants to cope with abiotic stress and combat competition with noxious and invasive weeds. Our research group is involved in investigating the role of root exudates in attracting beneficial soil microbes or deterring pathogens. Another aspect of our research is to investigate how water stress impacts the symbiotic relationship between soil bacteria -rhizobia and their ability to nodulate and fix N in crop plants.

Our laboratory uses several heterologous expression systems including Xenopus oocytes, E. coli, yeast, P. pastoris, tobacco cells, model, and crop plants to answer these research questions.

The second theme of 'Human Health' focuses on finding ways to limit aggressive invasiveness of Glioblastoma tumour cells (brain cancer). Glioblastoma is the most aggressive and invasive adult and paediatric cancer with a 15 month survival in adults and ~5 years in children post-diagnosis. Most research focuses on finding drugs that cause apoptosis of tumour cells, however the ability of these cells to evade treatment and become resistant leads to frequent tumour recurrence and invasion into healthy tissues. Very few researchers focus on limiting cell motility to control invasion of tumour cells. Our research focuses on inhibiting transporters and channels involved in cell motility and identifying novel natural compounds that can be used to limit tumour cell invasion. Limiting cell motility in recurrent tumours would lead to increase in therapeutic window for clinicians.

Projects

Selecting chickpea cultivars for growth and symbiotic performance under drought

Australia is second largest producer and exporter of chickpeas – a legume which is a good source of alternate protein globally. Despite its importance,  very little is known about how water stress affects nodulation and symbiotic N fixation. The purpose of the Grant is to select chickpea cultivars for growth and symbiotic performance under drought: improving yield and sustainability of chickpea production in India and Australia, by identifying high-performing lines with mutually low  water and nitrogen fertiliser requirements.

This project is conducted in collaboration between Flinders University researchers and Prof Varshney (Murdoch University), and Dr Kudappa (ICRISAT, India).

Increasing intrinsic heat tolerance of crop plants through improved genetics

Crop plants are susceptible to intrinsic changes in ambient temperatures that can affect important processes including growth, reproductive development and ultimately fertility and grain development. The aim of this collaborative project  is to develop low cost biomarkers that can be used by breeders and farmers to determine the sensitivity of crops to changes in temperature.

This project is conducted in collaboration with researchers at University of Adelaide, Flinders University & University of Melbourne.

Developing novel therapeutic candidates for limiting invasive capabilities of Glioblastoma multiform cells.

Glioblastoma Multiforme is an aggressive brain cancer with poor prognosis and survival. Tumours recur after treatment as cells develop resistance to chemotherapy, proliferate and aggressively invade resected and healthy brain tissues. Current research focuses on increasing sensitivity to chemotherapeutic drugs but not on limiting invasive capabilities of these cells. No pharmacological agents that target cell motility mechanisms are used currently as tools for limiting GBM invasiveness  during  eradication  treatments.  This  project  focuses  on  characterizing pharmacological compounds identified from a comprehensive screen of natural compounds sourced  from  Davis  Open  Access  Compound  library  that  effectively  inhibit  invasion  of glioblastoma cells.

This project is in collaboration with Prof Yool (University of Adelaide) and A/Prof Davis (Griffith University, QLD).

Testing combined therapies as a powerful tool for controlling paediatric Glioblastoma multiforme invasiveness.

Currently most treatments for cancers including GBM focus on either cell apoptosis or limiting cell division and proliferation as the primary outcomes for therapeutics. Few published studies have looked at pharmacological agents that target a combination of the ion channels, receptors and signalling pathways to effectively treat GBM motility. To thwart disease progression and improve overall survival, we need to discover new therapies and combinations of therapies targeting multiple pathways and create effective treatments with minimal toxicity for healthy cells. Limiting cell motility and invasion would be a powerful strategy to be used in conjunction with surgical resection, radiotherapy, and chemotherapy to improve prognosis and survival.

Work here will be the first to define the relative contributions of classes of ion channels as mechanisms promoting GBM cell motility in paediatric GBM. Pro-migratory mechanisms are a compelling therapeutic target for limiting GBM invasion and reducing tumour recurrence. These research outcomes could provide a platform for future translational studies that will limit GBM recurrence and improve survival in children.

This project is in collaboration with Prof Yool (University of Adelaide);  Prof Haberberger (University of Adelaide) and Ms Varricchio (University of Adelaide).

Funding Sources

Research Grants/Fellowships:

• Future Drought Fund, Long Term Trials, DAFF (2023-2028); $8M CI
• Grains Research Development Corporation (2023-2027); $1.9M CI
• Australia-India Council Grant (2022-2026); $160, 000; CIA
• Neurosurgical Research Foundation (2022-2023); $31,000; CIA
• Channel 7 Children’s Research Foundation (2022-2024); $91,000; CIA
• Australian Research Council (2019-2021; DP190101745); CIB

• 2019 Johannes Schwaries - PhD, University of Adelaide
• 2021 Suzanne Balacey - PhD, University of Adelaide
• 2022 Chethana Gowder-Shekharappa - PhD (Wine Australia Top up Scholarship); University of Adelaide
• 2021 Abolfazl Dashtbani Roozbehani - PhD, Flinders University
• 2023 Nick Booth - PhD, Flinders University
• August 2024 Mr Troy Miller - Research Excellence for PhD Thesis, Flinders University

Current Students

• Riley Hodgson - PhD; Flinders University
• Alexandra Cunningham-PhD; Flinders University
• Heidi Rogers - PhD; Flinders University
• Fatemeh Malekvandfard -PhD; Flinders University
• Kim Kristin Wagner - PhD; University of Adelaide

Advanced Medical Studies

• Vidia Hurudowar - MD; Flinders University

• Microbiology (1)