About NATi: The Nucleic Acid Therapeutics Initiative (NATi), hosted by A.STAR, is Singapore's national platform dedicated to advancing RNA-based medicines and transforming drug and vaccine development. NATi's mission is to establish Singapore as a globally recognised hub for nucleic acid therapeutics spanning discovery, clinical translation, and commercialisation.
NATi focuses on key RNA modalities including siRNA, antisense oligonucleotides (ASOs), and mRNA, and is building a biotech-style translational engine to drive target discovery, asset creation, and technology innovation across high-impact disease areas.
Position Overview: We are seeking an experienced Scientist / Senior Scientist - Target Discovery & Validation with deep expertise in human disease biology and target discovery to lead the identification and validation of novel targets druggable with RNA modalities for MASH, obesity, and skeletal muscle-related metabolic disorders. This role provides scientific leadership for early-stage target identification and validation using human genetics, multi-omics, and disease biology-driven approaches. The successful candidate will translate complex human datasets into actionable, prioritised targets suitable for siRNA/ASOdevelopment.
The successful candidate will bring his/her mechanistic understanding of liver, adipose, and skeletal muscle biology and the ability to interrogate and integrate large-scale human cohort data while working closely with bioinformaticians and computational biologists to deliver a high-quality, strategically aligned portfolio of novel targets.
Key Responsibilities
Lead Target Discovery: Own and advance a rolling portfolio of genetically and mechanistically supported targets for RNA therapeutics in MASH, obesity, and skeletal muscle related metabolic disorders, ensuring alignment with strategic and translational goals
Translate Human Data into Actionable Biology: Integrate human genetics and multi-omics datasets to generate clear, testable hypotheses, mechanistic rationales, and strategies that link target modulation to clinically meaningful outcomes.
Decision-Grade Target Selection: Establish and apply a standardised target ranking framework that supports transparent go / no-go decisions and reduces downstream attrition.
Cross-Functional Leadership: Serve as the scientific decision owner for target discovery, aligning bioinformatics, biology, and pharmacology teams around shared milestones and success criteria.
Define and Execute Target Enablement & Validation Strategies: Design and oversee fit-for-purpose validation plans using human-relevant models and RNA-compatible approaches to generate decision-enabling data for advancement or deprioritisation.
Human Disease Biology & Target Discovery:
Define disease-relevant biological questions in MASH, obesity, and/or muscloskeletaldisorders that guide data interrogation and hypothesis generation.
Identify causal or disease-modifying pathways across liver-adipose-muscle crosstalk and nominate intervention points amenable to modulation by RNA modalities.
Articulate mechanistic rationales linking target perturbation to clinically meaningful outcomes (e.g., fibrosis regression, insulin sensitivity, muscle function).
Target Output: Mechanism-of-action models disease pathway maps target biology briefs supporting investment decisions.
Multi-Omics & Human Genetics Integration:
Lead discovery efforts using GWAS, rare variant analyses, transcriptomics (bulk, single-cell, spatial), proteomics, metabolomics, and lipidomics.
Partner with bioinformaticians to design analysis plans, define statistical thresholds, and assess causality vs correlation.
Triangulate evidence across multiple human datasets to quantify confidence in target-disease relationships.
Target Output: Genetically anchored target dossiers reproducible analysis summaries evidence-weighted confidence scores per target.
Target Prioritisation & Clinical Relevance
Target Output: Ranked target lists with decision rationales documented go/no-go recommendations.
Target Enablement & Validation Strategy
Define fit-for-purpose enablement and validation plans for each advanced target, explicitly designed to demonstrate causal disease relevance and RNA-mediated druggability, specifying:
Human tissue and cell-based validation strategies to confirm target expression, regulation, and disease-associated activity in relevant liver, adipose, and skeletal muscle contexts
Genetic and molecular perturbation approaches (e.g., loss-/gain-of-function, pathway modulation) to establish directionality, mechanism, and downstream biological impact
Disease-relevant in vitro and in vivo models selected to test target engagement, pathway modulation, and phenotypic rescue
Ensure each prioritized target has clear predefined validation objectives, including clear mechanistic hypotheses, quantitative success criteria, and translational biomarkers that enable objective assessment of target validity and risk
Drive generation of decision-enabling validation data sufficient to support advancement into asset generation pipeline or formal deprioritisation
Target Output: Integrated target enablement and validation plans stage-gated validation roadmaps quantitative biomarker and readout strategies aligned to development and decision milestones.
Measures of Success
Percentage of nominated targets progressing into Asset Generation Pipeline
Strength and reproducibility of human evidence supporting advanced targets
Reduction in downstream attrition due to weak biology or poor translatability
Clarity and speed of target-related go / no-go decisions
Quality of cross-functional alignment and scientific decision-making
Qualifications & Experience
PhD in Biology, Genetics, Genomics, Bioinformatics, Pharmacology, or related discipline
A minimum of +5 (Scientist), +10 (Sr. Scientist) years of relevant experience in target discovery, human genetics, or translational disease biology in pharmaceutical and/or biotech organizations.
Proven expertise in multi-omic data interpretation and integration for complex human diseases
Strong background in metabolic disease biology, particularly MASH, obesity, and/or skeletal muscle disorders
Demonstrated experience working with bioinformaticians and computational biologists on large datasets
Track record of identifying, prioritising, and enabling novel therapeutic targets
Strategic, hypothesis-driven thinker with excellent scientific communication skills
Collaborative leader capable of influencing cross-functional teams in a matrixed environment
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.
