Scientist (Pharmacology), Cardiovascular & Metabolic Diseases Full-time

Scientist (Pharmacology), Cardiovascular & Metabolic Diseases

The Nucleic Acid Therapeutics Initiative (NATi), hosted by A*STAR, is Singapore's national platform dedicated to advancing RNA-based medicines and revolutionizing drug and vaccine development. NATi's mission is to establish Singapore as a globally recognized hub of excellence in nucleic acid therapeutics research, clinical translation, and commercialization. NATi focuses on key RNA modalities such as antisense oligonucleotides (ASOs), small interfering RNA (siRNA), and messenger RNA (mRNA). To drive this vision, NATi is building a biotech-like translational engine focused on asset and technology development spanning discovery to clinical development. We are actively seeking passionate and committed individuals with deep translational expertise to join us in advancing the next generation of RNA-based therapeutics.

Position Overview: We are seeking an execution-driven, hands-on Scientist (Pharmacology), Cardiovascular & Metabolic Diseases to support oligonucleotide discovery programs in obesity and MASH. This role is ideal for an MS-level scientist (10+ years of relevant experience) with strong bench depth who can own end-to-end in vitro cell-based mechanistic studies and in vivo rodent PK/PD studies generating complete data packages that support pipeline programs. While prior experience in RNA/oligonucleotide programs is desired, we care less about perfect modality match and more about proven hands-on pharmacology excellence. If you can run metabolic in vitro assays and in vivo mouse studies with rigor, NATi team can teach RNA/oligo-specific concepts and workflows.

Key Responsibilities

End-to-End Study Ownership (Core Expectation)

• Design and plan integrated in vitro and in vivo study strategies aligned to project questions
• Execute studies hands-on, ensuring appropriate controls, rigor, and reproducibility
• Analyse, interpret, and synthesize data into decision-quality outcomes
• Present clear conclusions and recommendations at internal project reviews
• Maintain timelines, anticipate risks, and troubleshoot methodically

Oligonucleotide Functional Pharmacology (In Vitro)

• Perform delivery/transfection of ASOs and siRNAs (training provided if needed)
• Execute dose-response and time-course studies to assess:
• Target engagement (mRNA/protein knockdown)
• Potency and durability
• Functional phenotypic outcomes relevant to obesity/MASH
• Evaluate off-target and cytotoxicity effects, and assay robustness

Metabolic Cell Models & Mechanistic Assays

• Culture and maintain primary and immortalized cell lines relevant to metabolic disease, including hepatocytes, myotubes, and adipocytes (e.g. HepG2, primary hepatocytes, C2C12, 3T3-L1)
• Develop and optimize in vitro models of steatosis, lipid metabolism, insulin resistance, and energy expenditure
• Lipid accumulation and steatosis assays (Oil Red O, BODIPY)
• Glucose uptake, insulin sensitivity, and fatty acid oxidation assays
• Mitochondrial respiration and bioenergetic profiling (e.g. Seahorse XF)
• Measurement of triglycerides, cholesterol, and inflammatory markers

Molecular Biology & Biomarkers

• RT-qPCR / qPCR for gene expression and knockdown assessment
• Western blotting for protein expression and signaling pathway analysis
• ELISA / Luminex for secreted metabolic and inflammatory biomarkers
• RNA/protein extraction, cDNA synthesis, and data interpretation

In Vivo Pharmacology and PK/PD (Hands-On)

• Develop, write, submit, and maintain IACUC protocols to support rodent in vivo studies, including new protocols, amendments, renewals, and compliance reporting
• Ensure all in vivo work is conducted in accordance with approved protocols, institutional SOPs, and animal welfare regulations
• Execute rodent efficacy studies in lean and diet-induced obese (DIO) mouse models
• Conduct dose-response, repeat-dose, and time-course studies using subcutaneous dosing (IV/IP/PO as required)
• Perform in-life metabolic assessments, including:
• oGTT / ipGTT, ITT, PTT, and other metabolic assessments as needed
• Metabolic cage studies (energy expenditure, RER, locomotion)
• Body weight, body composition, food intake, activity, and grip strength
• Monitor animals for tolerability, clinical signs, and overall animal welfare
• Execute PK/PD studies linking oligonucleotide exposure to target knockdown
• Collect blood and tissues (liver and other relevant tissues) for downstream analyses (e.g. PK exposure, RT-qPCR)
• Support tissue homogenization and bioanalytical workflows (e.g. for LC-MS/MS interface)
• Compile exposure-response relationships to support translational decisions

Data Integrity, Reporting & Compliance

• Perform quantitative data analysis using GraphPad Prism, Excel, ImageJ, and qPCR analysis tools
• Conduct appropriate statistical analyses (ANOVA, t-tests, EC50) and document assumptions
• Maintain rigorous electronic lab notebook (ELN) documentation and raw data traceability
• Prepare high-quality experimental reports and presentations for project updates and discussions
• Execute studies in compliance with IACUC protocols, institutional SOPs, and safety regulations

Qualifications & Professional Attributes

• Master's degree in Life Sciences, Pharmacology, Biomedical Sciences, or a related field
• Significant hands-on experience (10+ years) spanning both metabolic in vitro models/assays and rodent in vivo pharmacology (dosing, tissue collection)
• Demonstrated ability to plan, execute, analyze, and report studies with minimal supervision
• Direct experience developing, writing, and securing IACUC protocols (not only adherence) to enable in vivo studies
• Strong execution discipline: controls, documentation, reproducibility, data integrity
• Collaborative team player with strong communication skills and translational scientific thinking.
• Prior experience working with RNA modalities (siRNA/ASO) is desired but not required; NATi can train candidates with strong metabolic and in vivo pharmacology fundamentals