Principal Molecular Biologist

Mallinckrodt Pharmaceuticals
Robertson, Missouri, US
Apr 28, 2021
May 05, 2021
Employment Type
Full time
Salary Type

Mallinckrodt Pharmaceuticals is evaluating new generation siRNA therapies and is seeking a highly motivated and experienced Principal Scientist to join our team. Primary responsibilities will include design and execution of experiments to assess and optimize the medicinal chemistry of a novel class of therapeutic siRNAs, as well as testing drug candidates in a variety of in vitro and in vivo disease models. Candidates will be expected to work in a highly collaborative, creative and dynamic team environment. This senior position will require frequent updates to management and the ability to clearly identify and overcome obstacles that surface with the drug development process to nominate lead siRNA clinical candidates.

Essential Functions

The Principal Scientist will report to the Director of Cell & Molecular Biology and work in a matrixed environment with the medicinal chemistry, pharmacology, analytical chemistry, and pre-clinical teams. Responsibilities include, but are not limited to:

Working with internal development teams and external CROs, collaborators and consultants to guide chemical leads through developmental stage gates for candidate optimization and lead nomination.
Lead a diverse team of scientist in implementing molecular biology tools to define project plans for rapid siRNA optimization for clinical lead candidates for multiple targets.
A clear and proven track record of siRNA lead development from lead selection to pre-clinical models, toxicity studies and other essential NDA enabling activities for rapid clinical entry.
Experience with authoring critical NDA sections, product inserts and routine laboratory reports for FDA review is essential.
A clear understanding of siRNA delivery mechanisms, activity, stability, metabolism and off-target effects as demonstrated by publications through peer reviewed journals.
Must demonstrate proficiencies in siRNA design, modifications and targeting of siRNA.
Must demonstrate an understanding of the rapidly changing siRNA field, adjust, and remain current with innovations and technologies.
Development and execution of in vitro experiments measuring cellular uptake, stability, RNAi activity, selectivity, immunogenicity and other pharmacologic properties.
Development and execution of experiments elucidating MOA by measuring biological effects of RNAi constructs using cell line, primary cell, organoid, and tissue models.
Design experiments to understand targeted siRNA delivery to particular tissues and downstream efficacy and toxicity monitoring to achieve a satisfactory therapeutic window.
Assist with development and execution of cell-free and in vitro assays to measure medicinal chemistry properties such as RISC loading, protein binding, degradation and metabolism of lead and tool compounds.
Routine maintenance and generation of in vitro biological models required for the above.
Conducting routine analysis and interpretation of biological data and recommendations for further exploration to improve pre-clinical to clinical translation.
Writing study reports and maintaining accurate electronic records. Presenting data at internal/external meetings consisting of a matrixed team environment and external partners and consultants.
Maintaining organizational awareness of emerging siRNA technology and scientific developments, the regulatory landscape and competing commercial programs.
Providing scientific support for IP development.
Minimum Requirements

Education / Experience / Skills:

Education and Experience

PhD with 5 or more years of relevant siRNA industry experience as demonstrated with a publication record in the siRNA field.
Strong technical, analytical and time-management skills
Attention to detail, ability to innovate, aptitude for creative problem solving and bioanalytical acumen to navigate drug developmental stage gates
Willingness to take charge of and solve challenging technical issues while serving as the lead molecular biologist for multiple targets
Work with other technical leaders from medicinal and analytical chemistry and pharmacology to nominate clinical candidates and proceed with interactions with Regulatory, Quality, and Clinical liaisons
Strong desire to learn new skills and techniques for development of siRNA or other oligonucleotide therapeutics
Maintenance of epithelial and suspension cell lines and primary cells
Generation of stable cell lines with using viral vector
Transcriptomics experience a bonus
Knowledge in areas of inflammation, hepatic disease states a bonus
Tissue culture and cell-based assays (FACS, MTT, Staining, etc.)
Purification and quantification of RNA/DNA/protein, including qPCR and ELISA
In vivo experience with rodents, including animal handling, multiple routes of dose administration, blood collection, dissection techniques, and necropsies is a bonus
Technical skills:

Basic molecular biology (e.g. cloning, sequencing and genetic engineering)
Cell based assays: ELISA, luciferase, Northern, Western, flow cytometry
qRT-PCR and cellular transcriptomics
Fluorescence microscopy experience a strong bonus
Biology data analysis software: Excel, GraphPad Prism, FlowJo
Bioinformatics software: SnapGene

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