Project Description
This research aims to develop a novel HDAC inhibitor using molecular dynamics and docking software. The design will be based on our current lead compound, JRM-28. The target compound will be synthesized in our laboratory and evaluated through biological assays, including HDAC inhibition, toxicity testing, and microsomal stability. Subsequent behavioral studies will be conducted in mice. Methodology:
• Computational Design: Utilize molecular dynamics and docking software to identify HDAC inhibitors with high docking scores.
• Organic Synthesis: Prepare the lead compound in the laboratory based on computational predictions.
• Biological Assays: Measure histone acetylation levels to determine the compound’s effect on gene transcription related to memory formation.
• Toxicity & Pharmacokinetics: Determining toxicity profile and evaluating its ability to cross the BBB.
• Behavioral Studies: Administer the lead compound to mice via intraperitoneal injection and analyze effects on hippocampal-dependent spatial memory.
• Comparative Analysis: Evaluate efficacy and safety relative to romidepsin to assess therapeutic potential.
Tasks and Responsibilites
The student researcher will collaborate closely with graduate students and contribute to multiple aspects of the project, including:
• Computational Analysis: Identify promising compounds based on highest docking scores.
• Laboratory Techniques: Assist in organic synthesis, purification, and characterization of small molecules.
• Cell-Based Assays: Perform cytotoxicity tests on prostate cancer cell lines.
• Histone Acetylation Analysis: Conduct Western blotting or other biochemical assays to measure histone acetylation levels.
• Data Collection & Analysis: Record experimental results, assist with statistical analyses, and help interpret findings.
• Lab Maintenance: Prepare reagents, maintain lab equipment, and ensure proper sample handling.