Scientist, Bioinformatics

Emeryville, CA, United States

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4DMT is a clinical-stage biotherapeutics company harnessing the power of directed evolution for targeted genetic medicines. We seek to unlock the full potential of gene therapy using our platform, Therapeutic Vector Evolution (TVE), which combines the power of directed evolution with our approximately one billion synthetic AAV capsid-derived sequences to invent evolved vectors for use in our products. We believe key features of our targeted and evolved vectors will help us create targeted product candidates with improved therapeutic profiles. These profiles will allow us to treat a broad range of large market diseases, unlike most current genetic medicines that generally focus on rare or small market diseases.

We have built a deep portfolio of AVV-based gene therapy product candidates, with five product candidates in clinical trials: 4D-150 for the treatment of wet age-related macular degeneration (wet AMD) and diabetic macular edema (DME), 4D-710 for the treatment of cystic fibrosis lung disease, 4D-310 for the treatment of Fabry disease cardiomyopathy, 4D-125 for the treatment of X-linked retinitis pigmentosa (XLRP), and 4D-110 for the treatment of choroideremia. In addition, we have two product candidates in preclinical studies: 4D-175 for geographic atrophy (GA) and 4D-725 for alpha-1 antitrypsin deficiency.

To-date, we have demonstrated clinical proof-of-concept for three evolved vectors in three therapeutic areas and routes of administration with five products and patient populations. We believe this validates the power of our directed evolution platform for discovering superior vectors compared to wildtype viral vectors. We have built a robust and efficient product engine with 6 open Investigational New Drug Applications (INDs) in the U.S., 1 IND in Taiwan, and 1 Clinical Trial Approval (CTA) in Australia. We believe we are positioned to create, develop, manufacture and, if approved, effectively commercialize targeted genetic medicines that could transform the lives of patients suffering from debilitating diseases.

In addition to TVE, our technology includes a robust AAV manufacturing platform and onsite manufacturing facility that allows us to rapidly produce and test research grade material and scale up to GMP clinical material. This internal capability and close collaboration between our R&D and Manufacturing teams has greatly accelerated the pace of discovery at 4DMT.

Company Differentiators:

• Fully integrated clinical-phase company with internal manufacturing

• Demonstrated ability to move rapidly from idea to IND

• Five candidate products in the clinic and two declared pre-clinical programs

• Robust technology and IP foundation, including our TVE and manufacturing platforms

• Initial product safety and efficacy data substantiates the value of our platforms

• Opportunities to expand to other indications and modalities within genetic medicine

GENERAL SUMMARY:

As a Scientist on the Vector Innovation team, you will contribute to improvement and execution of our Therapeutic Vector Evolution platform, primarily through novel AAV library design, production, and screening in support of the discovery of novel therapeutic AAV vectors. You will work closely with the entire Vector Innovation & Human Cell and Disease Modelling team onsite to ensure our platform continues to yield best in class novel AAV capsids. Reporting to a Senior Scientist on the Vector Innovation team, you will primarily develop bioinformatics pipelines for NGS analysis and conduct computational biology experiments to solve problems in AAV engineering. Secondary to these responsibilities, you will work at the bench, contributing to data generation and validation of computational biology experiments.

RESPONSIBILITIES:

Bioinformatics & Computational Biology Development: 60% of TIME

Develop, optimize, execute, and maintain bioinformatics pipelines to process and analyze data from a wide range of experiments using high-throughput, next-generation sequencing

Independently develop reusable libraries and implement best coding practices to grow and improve 4DMT's bioinformatics & computational biology capabilities

Create user-friendly interfaces for bioinformatics pipelines and cross-train team members on their use

Manage internal experimental databases and code repositories

Perform project- and experiment-specific downstream data analyses in collaboration with cross-functional team members

Contribute to AAV vector library design and screening by designing and executing computational biology experiments

Provide ad-hoc bioinformatics and data science support and solutions for related projects and experiments, including quantitative microscopy image/video analyses, protein structure prediction/docking and analysis, and oligo pool design

Review literature to stay up-to-date on state-of-the-art AAV engineering and computational biology methods

Additional responsibilities as defined by management

Lab Activities: 20% of TIME

Provide support for internal sequencing services by contributing to library preparation and operation of sequencing instruments

Designing and validating materials used in NGS applications

Collaborate with Vector Innovation team members to ensure experimental design and execution are well-integrated with bioinformatics solutions

Contribute to the improvement and execution of AAV capsid screening and characterization experiments as needed

Additional responsibilities as defined by management

Meetings and Communication: 20% of TIME

Collaborate across R&D to identify areas of research that could be accelerated with computational approaches, and lead sourcing and implementation of those solutions

Effectively communicate complex analysis methods and results to colleagues and leadership

QUALIFICATIONS:

Education:

PhD in Bioinformatics, Genomics, Computer Science, or a related quantitative biology field

Candidates with MS or BS in similar fields and relevant industry experience are encouraged to apply

Experience:

PhD: 0-2 years of industry experience preferred

MS: 2+ years of industry experience required

BS: 5+ years of industry experience required

Skills:

REQUIRED:

Strong programming skills in Python and proficiency with commonly used libraries for biological data analysis (e.g., pandas, numpy, biopython, multiprocessing)

Experience developing custom, purpose-built bioinformatics tools and their integration into reproducible and reusable NGS analysis pipelines

Familiarity with usage and management of cloud computing resources (GCP preferred), Linux/Unix operating systems, and command line

Commitment to relevant best practices in software development, including version control, environment management, and documentation

Proficient in basic molecular and cellular biology techniques

ADDITIONAL/PREFERRED:

Knowledge of basic AI/ML principles and methods, and their application to biological problems

Strong data science and statistics/biostatistics background

Experience with containerization and workflow management (Docker, Singularity, Snakemake, Nextflow)

Basic UI development for scientific end users

Skilled in other programming languages

Background in AAV, viral vectors, directed evolution, high-throughput pooled screening, and/or protein/enzyme engineering

Base salary compensation range:

Bay Area Range: $130,000/yr - $155,000/yr

Please note that compensation varies based on experience, location, and other factors

4DMT provides equal employment opportunities to all employees and applicants for employment without regard to race, color, religion, gender, sexual orientation, national origin, age, disability, genetic information, marital status, status as a covered veteran, and any other category protected under applicable federal, state, provincial and local laws. Equal Opportunity Employer/Protected Veterans/Individuals with Disabilities

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