Senior Scientist
(Job Number: 210191)
Senior Scientist: Research Analytical Group
Overview
Alnylam is the world’s leading RNA interference (RNAi) company.
Founded in 2002, Alnylam was built upon a bold vision of turning scientific possibility into reality by harnessing the power of RNAi for human health as an innovative new class of medicines. We are a growing biopharmaceutical company with three approved medicines and a robust pipeline of investigational medicines focused in four strategic therapeutic areas: genetic medicines, cardio-metabolic diseases, infectious diseases, and central nervous system (CNS) and ocular diseases, including several in late-stage development.
Headquartered in Cambridge, Mass., Alnylam employs over 1,500 people in 19 countries and is rapidly growing globally, with additional offices in Norton, Mass., Maidenhead, U.K., Zug, Switzerland, Amsterdam, Netherlands, and Tokyo, Japan. Alnylam is proud to have been recognized as one of The Boston Globe’s Top Places to Work six years in a row (2015-2020), a Great Place to Work in the U.K. and Switzerland two years in a row (2019-2020) and a Science Magazine’s Top Employer two years in a row (2019-2020). Please visit www.alnylam.com for more information.
The Research Department at Alnylam is seeking a highly motivated (Senior) Scientist to lead the LC-MS analytical efforts of the evaluation of new siRNA conjugates for delivery to tissues extrahepatic (e.g., CNS, eye, muscle, kidney etc.) within the Research Analytical team and will report to the lead of said group. The successful candidate will need to apply a broad set of LC-MS and LC-MS/MS techniques, but also other analytical methods, to address primarily metabolism related questions for siRNA conjugated to small molecules, complex sugar molecules, peptides and various antibodies. He/she needs to have a solid understanding of assays and methods to address CMC and DMPK related questions needed to translate a successful new drug candidate into development. He/she will need to develop new methods, assays, and design studies to establish in vitro and in vivo metabolic stability of the novel conjugates using optimized extraction and LC-MS techniques. He/she will be the subject matter expert and further develop the LC-MS team by helping to design and improve the characteristics of siRNA-conjugates for drug candidate selection. In addition, the candidate will work closely with medicinal chemists, biologists, and toxicologists to evaluate the impurity profile, safety, and metabolic fate of successfully selected siRNA conjugates and transfer assays and methods to development for the successful manufacturing, characterization, and evaluation of their DMPK behavior.
Key capabilities
Analytical Thinker: Design, generate, and interpret complex data and apply knowledge to address chemical and biological questions; High attention to detail; Creativity, thinking out-side-the-box, developing fit-for-purpose solutions using a wide breath of analytical methods. Exceptional Communicator: Can understand, translate, and distill complex data into commentary and presentations that facilitate effective decision making within and across teams. Highly Collaborative: Actively engages and seeks out opportunities for collaboration across cross-functional teams; shares responsibility and credit; develops self and others through teamwork; comfortable providing guidance and sharing expertise with others to help them develop their skills and perform at their best. Leadership: Contribute as a leader to the Research Analytical team environment through superb communication, leadership, innovation, and passion. Passion: Capable of realizing the potential of fundamental scientific discoveries to quickly and flexibly move new discoveries from bench to bedside to continuously improve patients’ lives Influencer: Clearly articulates expectations, capabilities, and action plans; actively listens with others’ frame of reference; favorably influences people without direct authority. Role Model: Emulates the behaviors of Alnylam’s core values and fosters collaboration to lead and/or participate on high-performing teams. Proactive Self-Starter: Stays abreast of literature and industry activities to identify and evaluate new analytical techniques and assays; takes an active role in one’s own professional development
Summary of Key Responsibilities
Lead the LC-MS group a s a subject matter expert and develop members of the research analytical group by providing training, guidance, and mentorship. Integrate with the day-to-day operation of the research analytical group by appropriate prioritization of workload. Evaluate metabolism of siRNA designs encompassing novel chemistries using LC-MS techniques. Measure tissue levels, biodistribution and metabolic behavior of various novel conjugate siRNA designs to guide RNAi platform development. Develop and improve on LC-MS sensitivity utilizing micro- and nanospay LC-MS as well as improved sample preparation and extraction procedures from animal tissues. Improving methods for siRNA and siRNA-conjugates extraction from tissue, biological matrices and implement novel LC-MS strategies for identification. Effectively troubleshoot assays and instrumentation to find timely solutions. Implement novel analytical modalities to enhance detection limits. Analyze, interpret, and organize siRNA metabolism/analytical data to present at team and department meetings. Implement strategies for high-throughput generation and interpretation of metabolic stability data. Maintain strong commitment to high laboratory and scientific standards; the ability to maintain a safe, clean, and orderly laboratory work environment; good record-keeping and excellent laboratory documentation practice (electronic notebook), as well as assist in routine lab and equipment maintenance, vendor contracts, and requisitions is a must.
Qualifications
Ph.D. in Chemistry, Biology or a related field with 3-5+ years of experience in pharmaceutical/biotechnology industry. Subject-Matter-Expert in mass spectrometry and LC-MS and LC-MS/MS with hands on experience in the use and maintenance of high-resolution mass spectrometers is required. Previous experience with Thermo QExactive and Fusion instrumentation is a plus. Demonstrated experience in the LC-MS/MS quantification of peptides, small molecules and siRNA’s and their metabolites from animal tissue along with expertise in method development for the extraction of siRNA’s or siRNA-conjugates from biological tissue/matrices is essential. Know-how of samples cleanup techniques such as SPE, LLE immunoprecipitation etc. is necessary. Previous experience developing micro- or nano-flow LC-MS systems is a plus. Broad knowledge of analytical instrumentation along with familiarity of separation modalities such as IEX, RP, HILIC, SEC, affinity chromatography in a UPLC environment is expected. Excellent interpersonal skills along with ability to manage the LC-MS group within Research Analytics, by allocation of responsibilities and project prioritization, together with other cross functional team leaders is essential. Ability to work in cross-functional teams by analyzing, interpreting, and disseminating complex data is a must. Applicant must be self-motivated and excited to join a team working on analysis of new siRNA conjugate metabolism from in vitro and in vivo samples and development of novel assays. Excellent written and oral communication skills, good organization skills, the ability to multitask, and to work within a team and/or independently are required.
Alnylam Pharmaceuticals is an EEO employer committed to an exciting, diverse, and enriching work environment.