Junior Scientist / Scientist I (In Vitro Pharmacology), Cardiovascular & Metabolic Diseases

About NATiThe Nucleic Acid Therapeutics Initiative (NATi), hosted by A.STAR, is Singapore's national platform dedicated to advancing RNA-based medicines and revolutionising drug and vaccine development. NATi's mission is to establish Singapore as a globally recognised hub of excellence in nucleic acid therapeutics research, clinical translation, and commercialisation.

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 RNA scientists with deep translational expertise to join us in advancing the next generation of RNA-based therapeutics.

Position OverviewThe Junior Scientist / Scientist I (In Vitro Pharmacology), Cardiovascular & Metabolic Diseases will be responsible for investigating oligonucleotide-based modulation of key metabolic pathways in hepatic, skeletal muscle, and adipose cell models relevant to obesity, diabetes, and metabolic dysfunction-associated steatohepatitis (MASH). The role involves developing and optimising in vitro models of steatosis, lipid metabolism, and energy expenditure, as well as conducting adipocyte and myotube differentiation assays to study cellular and molecular responses. The scientist will perform oligonucleotide transfection, dose-response screening, and phenotypic characterisation using advanced molecular techniques such as qPCR, Western blotting, ELISA, and lipid droplet imaging. A strong understanding of metabolic signalling, mitochondrial bioenergetics, insulin resistance, and the pathophysiology of obesity, diabetes, and MASH is essential. The successful candidate will collaborate across discovery and functional genomics teams to deliver mechanistic insights and translational data supporting target validation and therapeutic development for metabolic diseases.

Key ResponsibilitiesCore Cell Culture Skills

• Aseptic technique and maintenance of sterile environments
• Culturing and sub-culturing of primary and immortalised cell lines (e.g. HepG2, C2C12, 3T3-L1, primary hepatocytes, myotubes, and adipocytes)
• Differentiation of pre-adipocytes to adipocytes and myoblasts to myotubes
• Transfection and transduction (lipid-based, electroporation, viral systems) of oligonucleotides (ASOs, siRNA, miRNA mimics/inhibitors)
• Cell viability, cytotoxicity, and proliferation assays (MTT, LDH, ATP-based assays)
• Functional assays for metabolic activity (lipid accumulation, glucose uptake, fatty acid oxidation)
• Cryopreservation and cell banking

Metabolic and Functional Assays

• Glucose uptake and insulin sensitivity assays
• Lipid droplet staining (Oil Red O, BODIPY) and quantification
• Mitochondrial respiration and bioenergetic profiling (e.g. Seahorse XF analysis)
• Measurement of triglycerides, cholesterol, and fatty acid content
• Inflammatory marker analysis in metabolic cell models
• Steatosis assay in hepatocytes

Molecular Biology Techniques

• qPCR / RT-qPCR for mRNA quantification and expression profiling
• Western blotting for protein expression and phosphorylation studies
• ELISA / Luminex assays for secreted proteins, cytokines, and metabolic biomarkers
• RNA and protein extraction, quantification, and quality assessment
• cDNA synthesis, primer design and plasmid cloning

Oligonucleotide Screening and Functional Evaluation (optional but desirable)

• Oligonucleotide delivery and dose-response studies
• Evaluation of target engagement via mRNA and protein level changes
• Data analysis for efficacy, potency, and off-target effects

Data Analysis and Documentation

• Quantitative data analysis using software such as GraphPad Prism, Excel, ImageJ, and qPCR data analysis tools
• Statistical analysis (ANOVA, t-test, EC50 calculations)
• Electronic lab notebook documentation and data traceability
• Preparation of experimental reports and presentations

Administrative Skills

• Procurement of reagents and consumables
• Maintenance of specialised research equipment
• Compliance with safety regulations
• Ad hoc duties as reasonably required during work

Qualifications & Experience

• Bachelor or Master's degree in Life Sciences or a related field.
• Minimum of 4+ (with a Master's degree) or 7+ (with a Bachelor's degree) years of relevant hands-on work experience in metabolic cell models, molecular assays (qPCR, Western blot, ELISA), and functional phenotyping, combined with a understanding of obesity, diabetes, and MASH pathophysiology.
• Cell culture & differentiation expertise - proven experience in culturing and differentiating skeletal muscle, and adipose cells, including primary cells and relevant immortalised lines.
• Metabolic & disease relevant assays - skilled in assessing steatosis, lipid metabolism, energy expenditure, insulin sensitivity, and mitochondrial bioenergetics in cellular models.
• Molecular biology techniques - proficient in qPCR, Western blotting, ELISA, and lipid staining, with strong data analysis and interpretation skill