| Project Id
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BRJP26100021
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| Project Detail
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| Project Title
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Harnessing multimodal systems to decode relationship between brain resident immune receptor expression, lipids, and vitamin D in neuropathological conditions
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| Senior Supervision Team (BITS)
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| Supervisor name and Title
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Dr. Pragya Komal
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School or Department (or company, if applicable)
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BITS PILANI, HYDERABAD CAMPUS
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Email ID
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pragya@hyderabad.bits-pilani.ac.in
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| URL for more info
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https://www.bits-pilani.ac.in/hyderabad/pragya-komal/
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| a) Are you currently supervising a BITS or RMIT HDR student?
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YES
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| Please comment how many you are supervising
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3
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| b) Have you supervised an offshore candidate before?
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NO
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| If no, what support structures do you have in place?
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| If yes, please elaborate
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N
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| Senior Supervision Team (RMIT)
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| Supervisor name and Title
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Dr. Sarah Spencer
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School or Department (or company, if applicable)
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STEM
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Email ID
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sarah.spencer@rmit.edu.au
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| URL for more info
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https://www.rmit.edu.au/profiles/s/sarah-spencer
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| a) Are you currently supervising a BITS or RMIT HDR student?
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YES
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| Please comment how many you are supervising
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9
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| b) Have you supervised an offshore candidate before?
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NO
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| If no, what support structures do you have in place?
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| If yes, please elaborate
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| Other Supervisors (BITS)
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| Supervisor name and Title
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School or Department (or company, if applicable)
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| Phone Number (Optional)
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Email ID
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| URL for more info
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| Other Supervisors (RMIT)
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| Supervisor name and Title
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School or Department (or company, if applicable)
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| Phone Number (Optional)
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Email ID
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| URL for more info
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| Field of Research (For Codes)
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| 310104~1181 | neurochemistry | 20.00 |
| 310901~1182 | animal behaviour | 20.00 |
| 320902 | basic neuroscience | 60.00 |
| 320903 | animal behaviour | 20.00 |
| 320905 | neurochemistry | 20.00 |
| 320999~1180 | basic neuroscience | 60.00 |
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| Project Description
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Neurological disorders and cognitive dysfunctions are among the leading causes of ill health, motor disability, and mental disturbances worldwide. In India, about 50,000 – 70,000 people suffer from Huntington’s disease (HD), with a prevalence in the range of 1/10,000–1/20,000 in the Caucasian population. Sadly, no treatment is available to stop the progression of the disorder. Also, globally, HD patients’ need related to mental and physical health is urgently required as people with mental disorders die prematurely and have excess motor and cognitive disability. The metabolic potential of the neurosteroid Vitamin D3 (VD) has recently attracted significant attention due to its beneficial actions against neurodevelopmental, neuropsychiatric, and neurodegenerative diseases. Previous findings from my lab have elucidated a neuroprotective effect of VD in HD (Manjari et al., 2022, 2023, 2024; Abraham et al., 2025). Hence, driven by the ultimate goal of promoting neuronal integrity and synaptic function, the present proposal aims to explore the impact of the neurosteroid Vitamin D3 on lipid metabolism and the expression of native immune receptors in HD. We will undertake in vitro and in vivo models to elucidate the effects of calcitriol on neuronal and non-neuronal gene expression (particularly in microglia and astrocytes) of the T-cell receptor beta subunit and enzymes involved in cholesterol and VD metabolism in HD. The specific methods of the project are as follows:
(1) Stable-inducible HEK293 cells expressing wild-type (Q23) and mutant (Q74) huntingtin exon one gene will be utilized for the given objective, and a dose-dependent effect of VD (calcitriol) will be performed in vitro.
(2) The stable inducible HEK293 cells expressing wild-type (Q23) or mutant (Q74) huntingtin (HTT) exon one gene and 3-NP mouse model will be used as described previously by Ashkenazi et al. 2017 and Manjari et al. 2023). Whole-brain tissue extraction will be performed for cholesterol profiling using the kit method.
(3) Investigate the effect of VD on the gene expression of key enzymes involved in cholesterol metabolic synthesis and determine the impact of VD on VDR expression on medium spiny neurons of the striatum in HD mice.
RATIONALE: The present work will explore the potential role of VD on brain cholesterol regulation and may be projected as a natural therapeutic strategy to rescue mutant protein aggregation and associated cognitive deficits in HD.
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| Project Deliverable/Outcomes
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Nutraceuticals over pharmaceutical interventions have the potential to rescue brain network dysfunction and combat neurodegeneration observed across myriad neurological disorders. HD is a progressive neurodegenerative disorder caused by a CAG triplet expansion in exon 1 of the huntingtin gene and leads to severe neuronal atrophy in the striatum and cortex. Unlike other neurodegenerative disorders, HD has limited symptomatic treatments for the movement and associated psychiatric problems. The polyglutamine expansion in the mutant huntingtin protein (mHTT) causes mitochondrial dysfunction, increased neuroinflammation, impairment in cholinergic neurotransmission, and oxidative stress, ultimately leading to the death of striatal neurons. The neurosteroid Vitamin D3 (VD) has recently been shown to have potential to preserve neuronal circuit function in age-related neurological disorders such as Huntington’s disease (HD). Cholesterol-based therapy has recently attracted significant attention in HD, where increasing cholesterol levels or stimulating its biosynthesis has been shown to enhance cognition in HD mice. Cholesterol is an important determinant of neuronal function and integrity, and its imbalance occurs in HD. Vitamin D3-mediated therapeutic strategies may be proposed to restore cholesterol homeostasis and decrease mutant HTT aggregation in HD by combating atypical expression of immune-native proteins, such as the T-cell receptor beta, in neuronal and non-neuronal cells of the CNS in neuropathological conditions.
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| Research Impact Themes
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| BETTER HEALTH OUTCOMES | AFFORDABLE HEALTH AND PREVENTABLE DISEASES |
| Life sciences | Molecular Biology |
| SUSTAINABLE DEVELOPMENT AND ENVIRONMENT
| SUSTAINABLE TECHNOLOGIES |
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| Which RMIT Sustainable Development Goal (SDG) does your project align to
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GOOD HEALTH AND WELLBEING
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| Which RMIT Enabling Impact Platform (EIP) does your project align to
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BIOMEDICAL AND HEALTH INNOVATION
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| Which RMIT Program code will this project sit under?
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| Student Capabilities and Qualifications
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Strong basic knowledge in the field of neuroscience and mental health is expected.
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Experience with animal handling, and maintenance of neuronal cell line, slice cultures, and non-neuronal cell lines will be preferred.
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MSc
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| Preferred discipline of Student
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| Biological Sciences |
| Biomedical Sciences |
| Biotechnology |
| Neurosceince |
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