Senior Scientist (RNA Therapeutics)

Role

In Vitro siRNA Screening & Drug Development for CNS Targets

Summary

We are looking for a highly motivated laboratory-based senior-level scientist to work in our preclinical drug discovery group where you will lead in vitro siRNA drug screening and development efforts. You will have responsibility for designing and delivering a diverse range of cell-based assays, providing critical data to help identify lead siRNA drug candidates for central nervous system (CNS) targets. You may also contribute towards the identification and validation of novel CNS drug targets. The ideal candidate will hold a PhD in Pharmacology, Molecular Biology, Neuroscience, or a related biological field, and have extensive laboratory experience in siRNA-based drug discovery. You will be able to demonstrate proven ability to plan, design, optimise and execute a wide range of cell-based assays and will also have direct hands-on experience in culturing and utilising mammalian cells including cell lines and primary cells.

Key Responsibilities

• Maintain and optimise mammalian cell cultures for siRNA screening workflows.
• Perform transfection of siRNA compounds using lipid-based, electroporation, or novel delivery methods, ensuring robust knockdown efficiency.
• Design and execute high-throughput siRNA screens using single-point and IC50 formats, employing bDNA or RT-QPCR assays for knockdown assessment.
• Understand pharmacological analysis and concepts of drug affinity and potency to aid lead compound selection.
• Assess siRNA conjugates for cellular internalisation, subcellular localisation (e.g., endosomal escape), and intracellular trafficking using imaging techniques (e.g., immunofluorescence, high-content imaging).
• Assess siRNA-mediated knockdown of target proteins using orthogonal methods such as Western blotting, ELISA, or MSD platforms to confirm functional silencing.
• Handle and prepare ex vivo biosamples from a variety of different biological tissues/fluids (e.g. serum/CSF/liver/brain) followed by quantification of mRNA and protein levels using various assays.
• Resolve technical challenges in biochemical/cellular assays
• Analyse, interpret, and upload screening data to electronic databases; maintain detailed documentation in lab notebooks.
• Present findings to cross-functional teams.
• Build strong networks – establish internal collaborations and identify and set up external collaborations.
• Design and execute drug project-related studies and workflows with external vendors/CROs to support drug projects.
• Show exceptional organisational skills with proven ability to manage multiple priorities and workloads.

Required Qualifications

• PhD in Pharmacology, Molecular Biology, or related discipline.
• 3+ years of post-PhD experience, ideally direct drug discovery experience in an industrial setting (pharma or biotech)
• Expertise in mammalian cell culture and transfection techniques (lipid-based, electroporation, viral vectors).
• Expertise in target knockdown assessment via bDNA assay, qRT-PCR, Western blotting and similar methods.
• Expertise in data analysis tools (e.g., RStudio, Prism)

Preferred Skills

• Strong demonstrable understanding of the preclinical drug discovery process.
• Experience with lead optimisation of siRNA therapeutics workflow.
• Experience culturing and utilising human iPSC-derived cells (neurons/glia).
• Experience with in vitro siRNA conjugate evaluation (e.g., ligand-targeted delivery).
• Familiarity with high-content imaging, automated screening platforms.
• Knowledge of neurodegenerative disease biology (e.g., Alzheimer’s, Parkinson’s).
• Experience in identification and validation of novel drug targets.
• Good working knowledge of basic bioinformatics software and implementation e.g. for sequence analysis and omics data analytics.