Scientist, Protein Sciences (fixed-term)

COMPANY & ROLE OVERVIEW

Kodiform Therapeutics is a discovery-stage spin-out from the Institute of Cancer Research and the University of Oxford, based on the pioneering research of our Founders, Professors Terry Rabbitts and Angela Russell. We develop small-molecule inhibitors of hard-to-drug proteins, including intrinsically disordered proteins, using our intracellular domain antibody (iDAb) platform. Our technology finds new functional binding sites on these proteins and opens new routes to target them with small molecules. We are based at the Scale Space science innovation hub in White City, London.

The role. We are looking for a protein scientist to join our small, multidisciplinary laboratory team on a fixed-term contract. Working hand in hand with colleagues in structural biology and pharmacology, you will clone, express, purify and quality-control the proteins at the heart of everything we do: our iDAbs and intrinsically disordered target proteins (full-length or as fragments) produced in bacterial and mammalian systems. These reagents power our platform, assays and structural studies, and ultimately our search for new medicines against proteins long considered hard to drug.

You will already have some hands-on experience of protein expression and purification (preferably nanobodies and or disordered proteins), and we will support you in building it further. You are organised, keep meticulous records and enjoy being part of a close-knit team.

We offer a competitive salary and pension.

PURPOSE & MISSION

This role will supply high-quality recombinant proteins to support Kodiform's intracellular antibody (iDAb) discovery activities. The postholder will design constructs for, express, purify and quality-control iDAbs and target proteins (full-length or domain fragments) from bacterial and mammalian expression systems. These reagents support library selection, binder characterisation, assay development and biophysical and structural studies on hard-to-drug proteins.

DIMENSIONS & STAKEHOLDERS

• Line manager [experienced protein scientist, biophysicist and structural biologist].
• Scientists team: iDAb platform, cell biology and assay development colleagues who use the proteins.
• External service providers and collaborators receiving protein (e.g. biophysics, mass spectrometry and structural biology CROs), through the line manager.
• Suppliers of reagents, gene synthesis and consumables.
• Laboratory Manager and Biological Safety Officer: laboratory operations, genetic modification (GM), biosafety and COSHH compliance.
• No direct reports and no budget responsibility.

KEY ACCOUNTABILITIES

Molecular biology

• Design and build expression constructs for iDAbs and target proteins or domain fragments (e.g. PCR, restriction, Gibson or Golden Gate assembly, site-directed mutagenesis), and verify them by sequencing.
• With guidance, choose construct features such as tags, fusion partners, protease sites, signal peptides, codon optimisation and domain boundaries.

Expression

• Express iDAbs and target proteins in E. coli (cytoplasmic and periplasmic) and in transient mammalian systems (e.g. Expi293/HEK293, ExpiCHO).
• Run small-scale expression and solubility screens, and scale up successful conditions.

Purification

• Purify proteins by affinity (e.g. IMAC, Protein A/G or other tag-based capture), ion-exchange and size-exclusion chromatography on automated systems (e.g. ÄKTA), including tag removal where needed.
• Optimise buffers and handling to keep proteins stable, including aggregation-prone and disordered targets.

Quality assurance and quality control (QA/QC)

• Carry out protein QC: SDS-PAGE, Western blot, concentration (A280), analytical SEC and intact mass (in-house or external). Use stability and aggregation methods (e.g. nanoDSF, DLS) and endotoxin testing where required.
• Confirm that iDAbs are functional by binding assays (e.g. ELISA, BLI or SPR).
• Release each batch against agreed specifications and record the results in a batch QC record or certificate of analysis.
• Register, aliquot, label and store protein stocks. Maintain the protein inventory and sample archive. Prepare samples and paperwork for shipment to partners.

General

• Keep meticulous records in line with company data-integrity standards.
• Communicate results at team meetings and in short written reports.
• Propose improvements to protocols and processes, e.g. yield, purity or throughput.
• Be an effective member of our laboratory team and contribute to the efficient running of the lab. This includes health and safety compliance (GM contained use, Containment Level 2, COSHH) and care of shared equipment, as well as contributions to lab housekeeping and maintenance of reagent stocks.

Skills

Essential

• Hands-on recombinant protein expression in E. coli.
• Protein purification by affinity and size-exclusion chromatography, ideally on an automated system (e.g. ÄKTA).
• Standard protein QC: SDS-PAGE, Western blot, concentration measurement.
• Core molecular cloning: PCR, cloning, plasmid preparation and sequence analysis (e.g. SnapGene, Benchling).
• Good aseptic technique.
• Strong organisational skills to manage multiple tasks, prioritise workload and meet project timelines.

Desirable

• Transient mammalian expression (e.g. Expi293, ExpiCHO) and mammalian cell culture.
• Periplasmic expression of antibody fragments.
• High throughput production of antibody fragments.
• Ion-exchange chromatography, tag cleavage or refolding.
• Biophysical methods, e.g. nanoDSF, DLS, BLI/SPR, analytical SEC or SEC-MALS.
• Interpretation of intact mass spectrometry data.
• Using electronic lab notebooks, LIMS or inventory systems.

Personal Qualities

Essential

• Team player.
• Highly organised, collaborative, detail-oriented approach.
• Meticulous record-keeping and commitment to scientific integrity and safe working.
• Willing to learn, and asks for help early when blocked.
• Enthusiasm to work in a dynamic research environment where priorities can change.

Desirable

• Proactive in suggesting improvements to methods and workflows.
• Confident communicating with external partners and suppliers.

Knowledge

Essential

• PhD in Biochemistry, Molecular Biology, Structural Biology or a related discipline; or an MSc/BSc in a relevant discipline with substantial relevant laboratory experience in industry [2+ years].
• Practical experience (e.g. PhD, postdoctoral or industry role) of producing recombinant proteins of a quality suitable for downstream assays.
• Understanding of protein structure, stability and quality-control principles.

Desirable

• Experience with VHH nanobodies, single-domain antibodies or other antibody fragments; knowledge of antibody structure and function would be desirable.
• Experience with difficult-to-express, multi-domain or intrinsically disordered proteins would be desirable.
• Producing protein for structural or biophysical studies (e.g. crystallography, NMR, HDX-MS, cryo-EM).
• Experience in a biotech or pharma setting, or interacting with CROs.
• Working under GM contained-use and Containment Level 2 conditions.
• Experience of high throughput protein production methods – especially antibody fragments.

Pay: £32,000.00-£48,000.00 per year

Benefits:

• Company pension
• Cycle to work scheme

Ability to commute/relocate:

• London W12 7RZ: reliably commute or plan to relocate before starting work (required)

Application question(s):

• Describe your experience with antibody production, engineering or screening, including any specific techniques or projects you've worked on.

Experience:

• relevant industry laboratory : 2 years (preferred)

Work authorisation:

• United Kingdom (required)

Work Location: In person