| Project Id
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BRJP26100112
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| Project Detail
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| Project Title
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Novel drug target identification and lead molecule development for neurodegenerative diseases
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| Senior Supervision Team (BITS)
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| Supervisor name and Title
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Aditya Sharma
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School or Department (or company, if applicable)
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BITS PILANI, DUBAI CAMPUS
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|
|
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Email ID
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aditya@dubai.bits-pilani.ac.in
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| URL for more info
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https://www.bits-pilani.ac.in/aditya-sharma
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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
|
1
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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?
|
|
| If yes, please elaborate
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N
|
| Senior Supervision Team (RMIT)
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| Supervisor name and Title
|
Taghrid Istivan
|
School or Department (or company, if applicable)
|
STEM
|
|
|
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Email ID
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taghrid.istivan@rmit.edu.au
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| URL for more info
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https://www.rmit.edu.au/profiles/i/taghrid-istivan
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| a) Are you currently supervising a BITS or RMIT HDR student?
|
YES
|
| Please comment how many you are supervising
|
2
|
| b) Have you supervised an offshore candidate before?
|
NO
|
| If no, what support structures do you have in place?
|
|
| If yes, please elaborate
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N
|
| Other Supervisors (BITS)
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| Supervisor name and Title
|
Debostuti Ghoshdastidar
|
School or Department (or company, if applicable)
|
BITS PILANI, DUBAI CAMPUS
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| Phone Number (Optional)
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+971 2753700 (422)
|
Email ID
|
debostuti@dubai.bits-pilani.ac.in
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| URL for more info
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https://www.bits-pilani.ac.in/dubai/debostuti-ghoshdastidar
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| Other Supervisors (RMIT)
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| Supervisor name and Title
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Dr Alexis Marshall
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School or Department (or company, if applicable)
|
STEM
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| Phone Number (Optional)
|
|
Email ID
|
alexis.marshall@rmit.edu.au
|
| URL for more info
|
|
| Field of Research (For Codes)
|
| 310112 | Structural Biology (incl. macromolecular modelling | 15.00 |
| 310199 | Biochemistry and cell biology not elsewhere classi | 35.00 |
| 310299 | bioinformatics and computational biology not elsew | 50.00 |
|
| Project Description
|
|
Neurodegenerative and neurodevelopmental disorders are responsible for significant global disease burden compounded by various factors like increasingly longer lifespans, social stigma, lack of awareness and access to adequate specialised support structures and therapy. Existing treatment modalities for these disorders, with unclear aetiology involving a complex interaction of genetic, environmental and lifestyle factors, focus mainly on symptomatic relief and are plagued with differential response rates among patients as well as low compliance rates. There is a very urgent need in the biomedical health sector to find new drug targets from novel pathways and develop orally available drugs which not only alleviate symptoms but improve quality of life and lead to a better prognosis.
Methodology - Analysis of publicly available OMICs datasets will be carried out in a hypothesis-free approach for mining differentially expressed genes or overrepresented pathogenic coding or splice variants for such diseases and mapping them to their respective genes. Further in silico analysis (gene enrichment, pathway analysis etc.) would be carried out to gain insights into the underlying pathophysiology of these disorders and uncover novel pathways as potential sources of drug targets. Prioritisation of these novel targets based on their suitability as a drug target, and their amenability towards computational drug design will be done through development of an automated, standardised pipeline with wider application, depending on scope of the project and appropriate collaborations. The top hits will be then taken forth for computer-aided drug design using a three-pronged approach: structure-based, ligand-based and de novo drug design, as well as drug repurposing to generate a few potential lead molecules with promising predicted binding affinity for the selected drug target(s). Various cheminformatics strategies including prediction of ADMET properties as well as pharmacokinetic and pharmacodynamic properties, energy minimization, MM-GBSA calculations and molecular dynamic simulations would be utilised for computational validation of the stability of the ligand-protein complexes of these top-hit molecules. These will be experimentally validated through in vitro preclinical studies.
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| Project Deliverable/Outcomes
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|
This project aims to use an interdisciplinary approach for development of novel, disease-modifying therapeutics for neurodegenerative (Alzheimer's, Parkinson's etc.) and neurodevelopmental disorders (Schizophrenia), utilizing computational OMICs and drug design as well as molecular modeling approaches, supplemented with experimental validation of drug efficacy and binding on selected targets. The key expected outcomes are as follows:
1) A ranked novel drug targets list and therapeutic strategies for neurodegenerative diseases (AD, PD)
2) An automated target prioritization pipeline for complex disorders
3) A portfolio of optimized lead molecules against the prioritized targets with corresponding binding affinity scores and structural interactions.
4) ADMET/Pharmacokinetics/Pharmacodynamics profiling for the top lead hits
5) Validated preclinical candidate dossier of lead molecules against the selected targets
6) Publications and dissemination, potential IP and commercialization of the novel targets and lead molecules
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| Research Impact Themes
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| BETTER HEALTH OUTCOMES | BIOTECHNOLOGY |
| Life sciences | Structural biology and drug design |
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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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|
DR231 PhD (App Biology & Biotech)
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| Student Capabilities and Qualifications
|
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Bioinformatics - CADD and molecular modelling, Programming, molecular biology techniques (cloning, protein purification etc.)
|
|
Python - pipeline development, Cell culture techniques
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|
MTech (preferred) or MSc
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| Preferred discipline of Student
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| Bioinformatics |
| Biological Sciences |
| Biology, Cell Biology, Niological Sciences |
| Biomedical Science and Biotechnology |
| Biotechnology |
| Genetics, Epigenetics, Genetic Engineering |
|