Scientist I/II - Cardiovascular & Metabolic Diseases Pharmacology (NATi)

About NATi The Nucleic Acid Therapeutics Initiative (NATi), hosted by A*STAR, is Singapore's national platform dedicated to advancing RNA-based medicines and accelerating drug and vaccine development. NATi aims to establish Singapore as a global hub for nucleic acid therapeutics by integrating target discovery, functional validation, translational pharmacology, and clinical development across key RNA modalities including antisense oligonucleotides (ASOs), small interfering RNA (siRNA), and messenger RNA (mRNA). Position Overview We are seeking a highly motivated, execution-driven Scientist with strong hands-on pharmacology expertise to support oligonucleotide discovery programs in obesity and metabolic dysfunction-associated steatohepatitis (MASH). This role is ideal for an BSc/MSc-level scientist with 10-12 years OR PhD with 7 years of relevant experience who can independently design, execute, analyse, and report integrated in vitro and in vivo pharmacology studies. While prior experience with RNA therapeutics is advantageous, candidates with strong metabolic pharmacology and rodent study expertise are encouraged to apply, as modality-specific training will be provided. Key Responsibilities Translational Pharmacology • Independently design and execute integrated in vitro and in vivo studies aligned with project objectives. • Generate high-quality, decision-enabling data through rigorous experimental design, troubleshooting, statistical analysis, and interpretation. • Present findings and recommendations at internal project meetings while maintaining accurate documentation and study timelines. In Vitro Functional Pharmacology • Perform ASO and siRNA transfection studies. • Conduct dose-response and time-course experiments to evaluate target knockdown, potency, durability, and functional outcomes. • Assess assay robustness, cytotoxicity, and potential off-target effects. Metabolic Cell Models • Culture and maintain relevant metabolic cell models, including primary hepatocytes, HepG2, C2C12 myotubes, and 3T3-L1 adipocytes. • Develop and perform mechanistic assays relevant to obesity and MASH, including: • • Lipid accumulation and steatosis (Oil Red O, BODIPY) • Glucose uptake, insulin sensitivity, and fatty acid oxidation • Mitochondrial respiration and bioenergetics (Seahorse XF) • Triglyceride, cholesterol, and inflammatory biomarker measurements Molecular Biology • Perform RT-qPCR/qPCR, Western blotting, ELISA/Luminex, RNA/protein extraction, and downstream molecular analyses to evaluate target engagement and pharmacodynamic responses. In Vivo Pharmacology & PK/PD • Develop, submit, and maintain IACUC protocols and ensure compliance with institutional animal welfare regulations. • Execute efficacy and PK/PD studies in lean and diet-induced obese (DIO) mouse models. • Perform rodent dosing (SC, IV, IP, PO), metabolic assessments (oGTT/ipGTT, ITT, PTT, metabolic cages), and monitor body weight, composition, food intake, activity, and tolerability. • Collect blood and tissues for pharmacokinetic, pharmacodynamic, and biomarker analyses, and support bioanalytical workflows. • Establish exposure-response relationships to guide translational decision-making. Data Analysis & Scientific Reporting • Analyze experimental data using GraphPad Prism, Excel, ImageJ, and qPCR analysis software. • Apply appropriate statistical analyses (e.g., t-tests, ANOVA, EC50) and maintain rigorous electronic laboratory records. • Prepare high-quality reports, presentations, and study documentation supporting project progression. Qualifications • Bachelor’s/Master's degree in Pharmacology, Biomedical Sciences, Life Sciences, or a related discipline with 10-12 years OR PhD with 7 years of relevant hands-on experience in vitro and in-vivo pharmacology. • Demonstrated expertise in study design, execution, troubleshooting, data analysis, and scientific reporting with minimal supervision. • Proven experience developing and managing IACUC protocols for rodent studies. • Strong understanding of experimental rigor, reproducibility, data integrity, and laboratory documentation. • Excellent communication, organizational, and collaborative skills with a translational research mindset. • Prior experience with RNA therapeutics (ASO/siRNA) is required. Experience in metabolic disease pharmacology is desirable but not essential. Candidates without prior expertise in metabolic disease indications are encouraged to apply and will receive comprehensive training. Global Recruitment & Competitive Compensation NATi is conducting a global search for top-tier talent in RNA therapeutics. We welcome applications from leading pharmaceuticals scientists and biotech innovators worldwide. This role provides a highly competitive compensation package aligned with global industry standards, including attractive benefits and long-term career growth opportunities within Singapore’s thriving biomedical innovation ecosystem. Join us in shaping the future of RNA-based medicines and establishing Singapore as a world-class hub for nucleic acid therapeutics. The above eligibility criteria are not exhaustive. A*STAR may include additional selection criteria based on its prevailing recruitment policies. These policies may be amended from time to time without notice. We regret that only shortlisted candidates will be notified.