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Job Title: Principal Scientist, Structure-based Ag Design

Location: Waltham, MA

About the Job

This role fills a global and critical vaccine research and development role for the Global Antigen Design/ Research and Development / Sanofi Vaccines global. The role is responsible for applying state-of-the-art structural biology methods, such as cryo-EM, to delineate atomic-resolution antigen/antibody structural models as basis for iterative structure-based vaccine design.

The role requires a PhD in structural biology or related fields with significant experience in cryo-EM. S/he will have an advanced understanding and practical experience with applying cryo-EM to solve novel viral and bacterial antigens in complex with monoclonal antibodies.

The incumbent will also be applying cryo-EMPEM to interrogate polyclonal antibody responses and identify critical protective epitopes. It is a major plus if the applicant also has experience in interfacing between computational and experimental sciences as well as extensive knowledge in preparing membrane protein complex and in-depth cryo-EM data processing for membrane protein and highly heterogeneous datasets.

This role reports directly to Head of Structure-based Antigen Design.

We are an innovative global healthcare company that helps the world stay ahead of infectious diseases by delivering more than 500 million vaccine doses a year. Across different countries, our talented teams are exploring new technologies to protect people and promote healthy communities. We chase the miracles of science every single day, pursuing progress to make a real impact on millions of patients around the world.

Main Responsibilities:

80%  General Job Duty – Structural Biology

• Perform cryo-EM sample preparation, data collection, data processing, and model building for viral and bacteria antigen/antibody complexes.

• Perform cryo-EM for vaccine designs going into clinical development.

• Perform cryo-EMPEM to map polyclonal antibody response for sera from vaccinated or infected individuals.

• Prepare sample for negative-stain EM and analyze results.                                                                                 

• Provide smart solutions for membrane protein purification using detergent, co-polymers, and/or liponanodiscs.          

• Process highly heterogenous cryo-EM datasets

• Interpret biophysical data for antigen-antibody complexes (e.g. ELISA, SPR, BLI etc) and protein quality/stability (e.g. SEC, DSF, DSC etc).

• Generate in-silico structural model using Alphafold or other protein modeling algorithms.

• Leads the investigation and development of next generation methods for structural biology. Acts as a subject matter expert in structural biology.

• Produces high-quality analyses that extend the capabilities and impact of the team as a whole.

• Generates IP and participates in the drafting of patent filings.

20% General Job Duty – Internal and External Networking

• Participates in relevant Project Teams and proactively maintain an open interface and communication channel with relevant areas of the company.

• Handle challenging tasks independently and can communicate well with the stakeholders and relay the key information back to structural biology team.

• Mentor junior team member in vaccine structural biology team and a key contributor in multiple project teams.

• Develops and maintains an international network of experts in structural biology, key science, technology and innovation areas, including outside the typical vaccine industry.

• Representations and interventions at the international/community level on relevant structural biology matters.

• Presents at conferences.

Context of the job / Major Challenges:
This position is key for achieving the mission of the Computational Antigen Design: pioneering, testing and implementing innovative cutting-edge biological science and novel Structural Biology/Machine Learning technology solutions and concepts towards antigen design.
The major challenges related to the role are:

• The complexity and variety of the role: ability to switch smoothly between different scientific and operational disciplines and requirements; being able to marry deep scientific research and fast exploratory mindset with proper documentation.

• Execute on a variety of timescales and parallel processes to accommodate requests from multiple projects.

• The need to quickly transform an idea into an experiment and learn from the result to decide on the next step, which might be to kill the idea.

• An unusually strong combination of biological science knowledge, structural biology knowledge, and physics knowledge.

• Tact, diplomacy, people skills, and excellent networking and communication (both oral and written) skills in general are important.

About You

Requirements:

• PhD in Molecular Biology, Biochemistry, Biophysics, Structural Biology, or closely-related discipline.

• More than 10 years postdoctoral training or industrial experience in structural biology is required.

• Experience with cryo-EM sample preparation and grid clipping is required.

• Experience with cryo-EM machines (Glacios and Krios) and familiarity with cryo-EM data collection software (SerialEM and EPU) is required.

• Experience with cryo-EM data processing (CryoSPARC and Relion) and model building (Coot, Phenix and other ML/AI-based method) is required

• Ability to independently design, plan and execute scientific studies, including operation and maintenance of relevant instruments and troubleshooting are required.

• Advanced skill in structural viewing program such as Pymol and ChimeraX is required.

• Experience with viral fusion protein and antibody biology is required.

• Experience with membrane protein biology is required.

• Experience with Alphafold3 and molecular dynamics simulation is preferred.

• A strong passion for empirical research and for answering hard questions with data

• Asymmetrical thinker who sees patterns of the big picture emerge from the parts. Creative brainstormer, skilled in divergent thinking. Ability to navigate ambiguity and interact effectively with unconventional people and ideas.

• Leading expert in membrane protein structural biology and can help biochemistry team to formulate and optimize cryo-EM ready membrane protein samples

• Highly flexible and adaptable individual able to thrive in a fast pace and ambiguous environment.

Why Choose Us?

All compensation will be determined commensurate with demonstrated experience. Employees may be eligible to participate in Company employee benefit programs, and additional benefits information can be found here.