Lata Vadlamudi

Personalising Epilepsy Regimes with Stem cells and artificial Intelligence models for Superior Treatment outcomes (PERSIST)

PERSIST, funded by the Medical Research Future Fund, is a new collaboration between the University of Queensland (QLD) and Monash University (VIC). We are now offering unique opportunities for trans-disciplinary honours/master/PhD research to students with background in neuroscience, cell biology, electrophysiology, machine learning, and clinical medicine. Students may be enrolled through either university, with opportunities to visit the other institution (depending on travel restrictions). Scholarships will be available for suitable students.

Epilepsy affects 1 in 26 people. Patients with recurrent seizures that may cause injuries or even death. Despite the development of many new medications over the last 20 years, more than 30% of patients do not have their seizure controlled. Currently it is not possible to predict which medications, either singly or in combination, will be effective for an individual patient, and no patient can trial all possible combinations within their lifetime. Under the current paradigm, the patient is sequentially trialled on different medications, doses and combinations in the hope of eventually finding an effective regime. For the patient this protracted (often years long) journey results in substantive co-morbidity, loss of productivity and greater risk of sudden death.

Instead of trial-and-error the PERSIST project will test a more personalised treatment strategy. The project aims to; a) use patient-specific induced pluripotent stem cell derived brain organoids to identify drugs that are able to modulate hyperactive neural activity, b) create an integrated predictive model for drug selection via artificial intelligence (AI) analysis of in vitro, clinical, and genomics data sets, c) validate treatment predictions in vitro and in real-world clinical care settings. The first part of this project will involve establishment of induced pluripotent stem cell lines from drug-resistant epilepsy patient blood samples and identify anti-seizure medications (ASMs) and drug combinations that suppress hyperactive neural activity in brain organoids derived from these cell lines. The second part of the project will involve integration of novel artificial intelligence approaches to further enhance the accuracy of these personalized drug efficacy profiles by incorporating single cell gene expression data sets, clinical information, and patient genomics data.

Women with epilepsy: The hidden burden of disease

Project outline

Epilepsy is a serious and common neurological condition, characterized by the recurring, unprovoked seizures, and affects around 25 million women worldwide. The World Health Organization highlight epilepsy as a public health imperative due to the substantive burden of disease, which is far greater than the seizures alone and includes psychiatric co-morbidity, decreased quality of life, fracture risk, loss of productivity and increased risk of death. Women face unique challenges due to changing sex hormone levels which can impact seizure burden and to date the role of hormones has been neglected in the care of women with epilepsy: perimenopause and beyond, evidenced by the lack of practice guidelines and consumer resources. This research strongly aligns with the vision of the 2020-2030 National Women’s Health Strategy to improve women’s health across their life course

This PhD will be aimed at generating new knowledge in these topics:

1. Developing a prospective, national, longitudinal database specifically looking at quality of life in women with epilepsy, cognition, bones and hormones in women with epilepsy in later life
2. Investigating the role of GABA-A receptor variants in women with epilepsy
3. Investigate the role of serum biomarkers (allopregnanolone) and genomic biomarkers in women with epilepsy
4. Develop clinical guidelines and consumer resources for women with epilepsy in later life
5. Build on the International Epilepsy in the Childbearing Ages through Menopause (ECAM) consortium

The Person

A medical degree plus undertaking advanced training in Neurology would be highly desirable as would be a strong desire to follow a clinician-scientist pathway. An honours or masters degree in biomedical science would also be considered.