Post-Doctoral Scientist – Mechanistic Modeling & Simulation(SMDD

At Lilly, the work is demanding because patients are waiting. We unite caring with discovery to help make life better for people around the world, knowing that every decision, every detail, and every day matters. Headquartered in Indianapolis, Indiana, our over 50,000 employees around the globe take on complex challenges to discover and deliver life-changing medicines, strengthen how health is understood and managed, and support the communities we serve.

This is hard, urgent, selfless work—but it’s work worth doing. If you’re driven by purpose and ready to bring your best to work that truly matters for patients, we invite you to join us.

As part of Lilly Research Laboratories, Synthetic Molecule Design and Development (SMDD) is a dynamic group made up of synthetic chemists, pharmaceutical scientists, analytical chemists, and engineers. We strive to identify, develop and apply groundbreaking technologies to deliver maximum benefit to our patients. Our team is looking for a creative and energetic chemical engineer to collaborate with a growing multidisciplinary team.

Aided with high-throughput experimentation and predictive thermodynamic tools, the engineer will use mechanistic modeling to develop a workflow to perform in-silico optimization of the biocatalytic assembly of oligonucleotides.

Traditionally, oligonucleotide therapeutics such as siRNA, ASO, and sgRNA rely on linear solid-phase oligonucleotide synthesis (SPOS), which is subject to yield, purity, and purification burden challenges as the sequence length increases. In contrast, a promising alternative is a convergent route where shorter oligonucleotide fragments are prepared via SPOS and joined together enzymatically. This enzymatic ligation (EL) approach has demonstrated superior yield, purity, and control of critical impurities as well as reduced environmental impact compared to SPOS.

As a result, this approach has generated significant interest from the pharmaceutical industry as exemplified by numerous patents, publications, and conference presentations. Whereas the elementary steps of the ligation reaction have been elucidated in the literature using wild type enzymes, much more is to be understood to enable the development of a scalable and versatile synthesis platform that gets genetic medicines to patients faster.

This postdoctoral position offers the opportunity to build a predictive mechanistic model of enzymatic ligation kinetics, generate process understanding that has previously been limited to qualitative trends, and accelerate EL process development. This project will also leverage high-throughput experimentation capabilities at the Lilly Seaport Innovation Center in Boston to parameterize thermodynamic and kinetic models of oligonucleotide assembly and ligation. The project provides the chance to collaborate not just within SMDD, but also discovery and development teams on multiple genetic medicine modalities across Boston and Indianapolis sites.

The prestigious Lilly Research Laboratories (LRL) post-doctoral program funds challenging and innovative projects in the pre-competitive space with the expectation of external publication and presentation. LRL post docs receive mentorship from leading scientists at Lilly as well as the opportunity to network with other scientists in the program. The post-doc project is expected to result in scientific publications as well as computational workflows for internal process development.

• Initiate collaborations across and beyond the SMDD organization to pioneer a multi-disciplinary approach to accelerating process optimization via computational tools
• Understand and prioritize key challenges in process development via interactions with diverse talent across the larger organization.
• Demonstrate independence, self-motivation, and high learning agility regarding grasping and exploiting new scientific concepts and methods.
• Engage the external environment through presentation of findings at conferences and publishing in high-quality peer-reviewed journals.
• Embrace diversity of thought, background and experience to deliver…