Research Scientist

Understanding the dynamic three-dimensional spatial patterns of gene expression is essential for elucidating the mechanisms that drive tissue development and disease. To address this challenge, the Sharpe lab developed Cell 3D Positioning by Optical Encoding (C3PO), an innovative methodology that preserves three-dimensional positional information from intact biological tissues prior to dissociation. By embedding spatial coordinates directly within cells using controlled optical encoding, C3PO enables reconstruction of spatial molecular landscapes from complex tissues. The approach integrates advanced mesoscopic imaging, tissue biology, and downstream omics workflows, leveraging the multidisciplinary expertise within the lab to generate spatially resolved snapshots of biological organisation. In its initial application, C3PO was combined with transcriptomic readouts to reconstruct spatial gene expression landscapes in developing mouse limb buds, providing insight into how cellular identity and function are organised within this complex biological system. Importantly, C3PO is technology-agnostic and can be integrated with a wide range of downstream molecular assays, including genomic, transcriptomic, and proteomic approaches.

The current project will extend the application of C3PO into an exciting translational direction in oncology, where its ability to quantify spatial heterogeneity across intact tissue volumes in 3D offers significant clinical potential. Tumour architecture and microenvironmental organisation play critical roles in disease progression and therapeutic response, yet remain difficult to capture using conventional molecular approaches that rely on two-dimensional tissue sections. By preserving spatial information prior to tissue dissociation, C3PO enables three-dimensional molecular profiling at defined spatial voxel resolution across clinically relevant tissue volumes. Specifically, this project will apply C3PO in oncology across three key areas:

Quantification of tumour cell heterogeneity, supporting both fundamental cancer research and the development of potential companion diagnostics (CDx) for improved patient stratification and personalised medicine approaches. Spatial mapping of neoantigen distribution within tumours to prioritise targets that are broadly represented across tumour tissue, supporting development of more effective immunotherapeutic strategies and enabling potential companion diagnostic (CDx) applications. Measurement of T-cell infiltration following immunomodulatory therapies designed to convert immunologically “cold” tumours into “hot” tumours, enabling assessment of therapeutic response as a Companion Response Marker (CRM) and supporting biomarker development.

Responsibilities

Project & Operational Responsibilities

• Coordinate execution of the C3PO oncology project across internal research teams, institutional core facilities, and external collaborators, requiring strong organisational and interdisciplinary communication skills.
• Translate project objectives into detailed experimental workplans aligned with defined milestones and deliverables.
• Track progress against timelines, identify technical risks, and implement mitigation strategies using structured project management approaches.
• Coordinate access to specialist infrastructure including mesoscopic imaging platforms, flow cytometry instrumentation, and sequencing services.
• Liaise with clinical collaborators, biobanks, and technology specialists to ensure timely access to biological materials and technical expertise.
• Contribute to preparation of further funding applications, technical documentation, and materials supporting future translational development or commercialization.
• Provide technical supervision and training to junior researchers or students in molecular biology, tissue processing, and quantitative experimental workflows.
• Maintain clear documentation of experimental progress and ensure effective knowledge transfer within the project team.

Research & Technical Responsibilities

Biological sample acquisition and preparation

• Identify and coordinate sourcing of appropriate biological materials including human tumour samples, patient-derived xenografts (PDX), mouse tissues, embryonic samples, and organoids.
• Apply knowledge of tissue biology and experimental design to select appropriate sample types for investigating tumour heterogeneity, neoantigen distribution, and immune cell infiltration.
• Perform tissue preparation workflows including fixation, staining, embedding, and preparation of intact tissue samples for optical encoding.
• Ensure compliance with ethical requirements and proper documentation for handling human and animal-derived tissues.

Optical encoding and imaging workflow development

• Implement and optimise C3PO optical encoding protocols using advanced mesoscopic imaging platforms.
• Design and troubleshoot multi-axis photobleaching strategies to generate reproducible spatial barcode gradients.
• Apply quantitative understanding of fluorescence imaging and photophysics to optimise signal-to-noise ratios and spatial resolution.
• Work closely with imaging specialists to refine acquisition and bleaching parameters for cm³-scale biological samples.

Tissue dissociation and single-cell workflows

• Develop and optimise mechanical and enzymatic tissue dissociation protocols suitable for large and structurally complex tissue samples.
• Apply experience with single-cell workflows to maximise cell recovery and maintain representative sampling of heterogeneous tumour tissues.
• Perform experimental validation of dissociation protocols using appropriate controls and quantitative quality metrics.

Flow cytometry and spatial decoding

• Design and implement flow cytometry (FACS) workflows for acquisition of optical barcode information from dissociated cells.
• Optimise multi-channel fluorescence detection and gating strategies to enable robust spatial reconstruction of tissue architecture.
• Apply quantitative analysis approaches to evaluate fluorescence ratios and ensure reproducibility of spatial encoding measurements.

Library preparation and sequencing workflows

• Develop and optimise RNA sequencing and DNA sequencing library preparation protocols incorporating cellular barcodes and unique molecular identifiers (UMIs).
• Implement combinatorial indexing strategies to increase throughput and scalability of spatial omics experiments.
• Adapt transcriptomic and immune repertoire sequencing workflows to quantify tumour heterogeneity, neoantigen distribution, and T-cell clonality.
• Ensure high-quality sequencing libraries through appropriate experimental controls and troubleshooting of protocol inefficiencies.

Data analysis and interpretation

• Analyse spatial omics datasets including transcriptomic and immune repertoire sequencing data using appropriate bioinformatic tools.
• Contribute to development and refinement of computational pipelines for spatial reconstruction based on optical barcode information.
• Interpret spatial patterns of gene expression, tumour heterogeneity, neoantigen distribution, and immune cell infiltration.
• Maintain well-structured datasets and ensure reproducibility of analysis workflows.

Communication & Scientific Reporting

• Prepare clear scientific reports, figures, and presentations describing experimental findings and technical developments.
• Contribute to preparation of manuscripts describing methodological advances and biological discoveries enabled by C3PO.
• Communicate complex interdisciplinary concepts effectively across molecular biology, imaging, computational, and clinical collaborators.
• Present project updates at internal meetings and external scientific events where appropriate.
• Contribute to preparation of documentation supporting intellectual property development and technology translation.

Compliance, Quality Control & Laboratory Management

• Ensure experimental work complies with institutional ethical regulations, biosafety requirements, and data management policies.
• Maintain detailed laboratory records, protocols, and metadata consistent with reproducibility standards.
• Implement quality control procedures across imaging, molecular biology, and sequencing workflows.
• Manage laboratory inventory of reagents, consumables, and biological samples.
• Contribute to development and implementation of standard operating procedures (SOPs) for C3PO workflows.
• Maintain safe laboratory working practices in accordance with institutional health and safety guidelines.

Skills, Experience and Expertise Required

Essential

• PhD (or equivalent experience) in molecular biology, developmental biology, bioengineering, genomics, or a related discipline.
• Experience with fluorescence microscopy or advanced mesoscopic imaging techniques.
• Strong experimental background in molecular biology techniques such as RNA extraction, cDNA synthesis, PCR, and next-generation sequencing library preparation.
• Experience working with complex biological tissues, including tissue processing, dissociation, and preparation for single-cell analysis.
• Experience with flow cytometry or FACS-based experimental workflows.
• Quantitative and analytical mindset with experience handling high-dimensional biological datasets.
• Experience troubleshooting and optimising experimental protocols.
• Ability to manage complex multi-step experimental workflows with attention to detail.
• Strong organisational and project coordination skills.
• Ability to communicate effectively across interdisciplinary teams.
• Experience maintaining clear and reproducible experimental documentation.

Highly desirable

• Experience with spatial transcriptomics or single-cell sequencing technologies.
• Familiarity with bioinformatic workflows for RNA-seq or immune repertoire sequencing.
• Experience working with tumour biology, immunology, or developmental biology systems.
• Experience implementing experimental barcoding strategies or combinatorial indexing approaches.
• Familiarity with handling human clinical samples or working with biobanks.
• Experience contributing to collaborative interdisciplinary research projects.
• Interest in translational research and technology development.

Other helpful information 

Contract length: 1 years (project related)

Salary: Grade 7

We are committed to open and fair recruitment practices. We would like to be transparent that internal candidates with required relevant experience will be prioritized for consideration and assessment.

Why join us

EMBL is curiosity-driven, community-oriented and international. As an inclusive, equal opportunity employer, we believe that diversity enables us to collaborate more effectively and be innovative in our approaches. We are, therefore, committed to creating an inclusive and flexible culture - one where everyone can realise their full potential and make a positive contribution to our organisation. 

We encourage applications from individuals who can complement our existing team – we believe that success is built on having teams whose backgrounds and personal experiences reflect the diversity of the populations that our science serves. We actively encourage applications from all genders and cultures, ethnic groups and all demographics to help us avoid perpetuating biases and oversights at this transformational point in our people strategy.

Enjoy lots of benefits:

• Financial incentives: Salary free of income tax, Monthly family, child and non-resident allowances, annual salary review, pension scheme, death benefit, long-term care, accident-at-work and unemployment insurances

• Flexible working arrangements

• Private medical insurance for you and your immediate family (including all prescriptions and generous dental & optical cover)

• Generous time off: 30 days annual leave per year, in addition to public holidays

• Relocation package including installation grant (if applicable)

• Campus life: Free shuttle bus (Heidelberg), library, subsidised on-site cafeteria, casual dress code, extensive sports and social club activities (on campus and remotely)

• Family benefits: Kindergarten (Heidelberg), 10 days of child sick leave, generous paid maternity/parental leave and monthly family & child allowances

• Benefits for international newcomers: Visa exemption, education grant for private schooling, financial support to travel back to your home country every second year and a monthly non-resident allowance.

• For detailed information please visit our employee benefits page here

What else you need to know

• International applicants: We recruit internationally and successful candidates are offered visa exemptions. Visit our International Applicants page, to find out more.

• EMBL is a signatory of DORA. Find out how we apply DORA principles to our recruitment and performance assessment processes here.

• Diversity and inclusion: At EMBL, we believe that diverse teams drive innovation and scientific excellence. We encourage applications from candidates of all genders, identities, nationalities and/or any other diverse backgrounds.

• How to apply: To apply please submit a cover letter and a CV through our online system. Applications will close at 23:59 CET on the date shown below. We aim to provide a response within two weeks after the closing date.

Closing Date