Senior Scientist_

Waltham

**About the Job**

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.​

**SUMMARY**

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 techniques such as cryo-EM and computational tools to design potential vaccine for infectious diseases and self-antigens. The role requires a PhD in structural biology or computational biology or biophysics or related with significant experience in rational protein engineering. S/he will have an advanced understanding and practical experience with applying structural biology and computational biology toolbox to design antigens in their functional states. The incumbent will also be applying novel AI-based and/or physic-based programs to design vaccine antigens and optimize antigen display on a variety of platforms. Successful candidate should also have decent level of knowledge regarding host-pathogen interactions and human immunology. It is a major plus if the applicant also has experience in interfacing between computational and experimental sciences. This role reports directly to Global Head of Computational Antigen Design.

**DUTIES**

**70% General Job Duty– Structure-based & de novo designs for novel antigens**

+ Perform structure-based protein engineering and optimize antigen display on a variety of platforms by using **_Schrödinger, MOE, Rosetta and other computational tools._**

+ Design novel self-antigens by using Deep ML-based tools such as ProteinMPNN or LLM-based tools such as ESM fold and physic-based programs

+ Design novel antigens that can carry both conformational B cell epitopes and common T cell epitopes

+ Design novel antigens that has minimal off-target immunogenicity

+ Design biophysical and biochemical experiments to interrogate the soundness of the designs. For instance, using SPR or BLI etc to assess antibody affinity to designer antigens and using SEC-MALS, DSF, DSC, DLS, Mass Photometry etc to assess antigens’ quality/stability/oligomerization states

+ Familiar with B-cell immunology e.g. B-cell activation in germinal center, clonal expansion and affinity maturation.

+ Leads the investigation and development of next generation methods for computational biology

+ Acts as a subject matter expert in protein engineering

**20% General Job Duty– Structure determination using cryo-EM or X-ray crystallography**

+ Perform CryoEM sample preparation, data collection, data processing, and model building for viral and bacteria antigen/antibody complexes and self-antigens

+ Perform CryoEM for vaccine designs going into clinical development.

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

+ Generate structural models of self-antigens in specific conformations by using computational tools

+ Serves a key interface between structural biology and ML teams, and a key representative and interface among global antigen design and global immunology

+ 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.

**10% 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.

+ Ensures transparent and cooperative liaison with other positions around innovation and artificial intelligence/big data within the wider Sanofi Group.

+ Ensures efficient and agile communication of key information, process and workflow operational element in various circumstances.

+ Leads by Influence to mentor diverse staff in the interpretation and generation of novel vaccine candidates performance data.

+ 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.

**REQUIREMENTS**

+ PhD in Computational Biology, Biophysics, Structural Biology, or closely-related discipline.

+ A background in structural biology and computational biology is required.

+ Experience with _Schrödinger, MOE_ or Rosetta 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 model building (Coot and Phenix, Isolde) 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 Alphafold 3 and molecular dynamics 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.

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

+ Ability to process multiple inputs to develop a clear understanding of a problem, issue or potential solution and translate them into practical business opportunities.

+ Excellent analytical and problem-solving as well as communication, scientific writing and presentation skills. Ability to put together a convincing business case.

+ Excellent communication skills.

**Why Choose Us?**

+ Bring the miracles of science to life alongside a supportive, future-focused team.

+ Discover endless opportunities to grow your talent and drive your career, whether it’s through a promotion or lateral move, at home or internationally.

+ Enjoy a thoughtful, well-crafted rewards package that recognizes your contribution and amplifies your impact.

+ Take good care of yourself and your family, with a wide range of health and wellbeing benefits including high-quality healthcare, prevention and wellness programs and at least 14 weeks’ gender-neutral parental leave.

Sanofi Inc. and its U.S. affiliates are Equal Opportunity and Affirmative Action employers committed to a culturally diverse workforce. All qualified applicants will receive consideration for employment without regard to race; color; creed; religion; national origin; age; ancestry; nationality; marital, domestic partnership or civil union status; sex, gender, gender identity or expression; affectional or sexual orientation; disability; veteran or military status or liability for military status; domestic violence victim status; atypical cellular or blood trait; genetic information (including the refusal to submit to genetic testing) or any other characteristic protected by law.

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