Scientist II

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Job description

Attention recruitment agencies: All agency inquiries are vetted through 4DMT's internal Talent Acquisition team. No unsolicited resumes will be accepted. The 4DMT Talent Acquisition team must expressly engage agencies on any requisition. Agencies contacting hiring managers directly will not be tolerated, and doing so may impact your ability to work with 4DMT in the future.

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.

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 II on the Payload Innovation team, you will contribute to the development and discovery of novel Therapeutic Payload elements and the evaluation of these Payload Constructs through payload elements database construction, candidate screening and novel assay development. You will work closely with the Emerging Technology and Early Product development teams to ensure that the novel payload construct meets the product development requirements. Reporting to a Director in the Payload Innovation team, you will execute bioinformatics pipelines to identify potential payload construct candidates and conduct laboratory experiments to screen these candidates and propose lead candidates for downstream product development. Secondary to these responsibilities, you will develop different NGS and other molecular biology assays for payload construct evaluation.

RESPONSIBILITIES:

Lab activities: 60% of TIME

• Build genetic regulatory element databases through identification of existing tissue specific database in the literature and through next-generation sequencing with primary tissue samples

• Execute screening strategies to evaluate novel payload constructs in a high throughput manner, plan and perform prove-of-concept experiments to validate the screening strategies

• Utilize molecular biology software to construct payload plasmid design, leverage modem cloning techniques to build these constructs in a high throughput manner, validate cloning results with various sequencing techniques

• Maintain various mammalian cell cultures including immortalized cell line and primary cells, apply different techniques to introduce non-endogenous nucleic acid sequences into the target cell types

• Evaluate payload construct performance in desired cell types by executing and developing molecular and cellular assays, such as ELISA, flow cytometry, ddPCR and single cell multi-omics

• Provide other ad-hoc laboratory supports for related projects and experiments based on the team priority

• Execute good record keeping practices, ensure experiments and data are reproducible and trackable

• Review literature to stay up-to-date on state-of-the-art AAV therapeutic payload development

• Additional responsibilities as defined by management

Computational and Scientific Administrative Tasks: 30% of TIME

• Perform data analysis for assays and experiments to characterize different payload construct developments efforts

• Execute computational pipeline to analyze large dataset and build internal payload component databases

• Design experiments for payload construct evaluation, experiment strategy validation or assay development purposes

• Compare and evaluate external vendor to provide computational and AI/ML support for various projects

• Propose troubleshooting approaches for specific experimental processes

• Payload design and experimental material inventory maintenance

• Additional responsibilities as defined by management

Meetings and Communication: 10% of TIME

• Participate in departmental meetings and project team meetings to understand cross-functional requests and share scientific findings

• Collaborate across Non-Clinical Organization to identify areas of research that could create novel payload development opportunity, and propose research plan to investigate these options

• Effectively communicate complex experiment results to colleagues and leadership

QUALIFICATIONS:

Education:

• PhD in Molecular Biology, Biochemistry, Bioengineering, Cell Biology, or related field

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

Experience:

• PhD: 3+ years of industry experience preferred

• MS: 8+ years of industry experience required

• BS: 10+ years of industry experience required

Skills:

REQUIRED:

• Strong track record of developing therapeutic payload constructs and evaluate them with molecular and cellular biology techniques

• Molecular cloning, nucleic acid manipulation and purification

• Mammalian cell culture, plasmid transfection and viral transduction

• Experience with common molecular and cellular assays such as ELISA, ddPCR, flow cytometry, NGS, single-cell sequencing

• NGS library preparation and sequencing instrument operation

• Basic bioinformatic knowledge, execution of established computational pipelines

• Familiar with AAV biology, gene therapy, virology, high throughput screening and assay development

ADDITIONAL/PREFERRED:

• Experience with high-throughput pooled or array screening methods

• Build customized NGS solution to solved particular biological problems

• Experience developing protocols for automated liquid handlers

• Tissue processing and library preparation for single-cell multi-omics

• Skilled in common bioinformatics programming languages such as Python and R

Base salary compensation range: $139,000 - $184,000

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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