RNA splicing is highly dysregulated in cancers, creating novel opportunities for therapeutic intervention by targeting key nodes of the RNA processing pathway. Marlinspike Therapeutics has developed a functional genomics and computational biology platform to identify cancers that are vulnerable to targeting RNA splicing and define molecular targets that exploit these vulnerabilities. In addition to tumor-intrinsic dependencies, recent work from our academic founder Professor Thomas (‘Trey’) Westbrook from Baylor College of Medicine, has revealed that targeting splicing in certain cancers can activate powerful anti-tumor immune pathways.
Marlinspike has brought together a powerful platform underpinned by unique synthetic lethality screens in relevant biological contexts to identify key cancer vulnerabilities. To rapidly target these vulnerabilities, Marlinspike uses an integrated modern medicinal chemistry platform spanning: biochemistry, structural biology, molecular dynamics, and medicinal chemistry to develop both covalent and non-covalent modulators. Marlinspike Therapeutics has established a state-of-the-art laboratory in Cambridge, MA, and is funded through Series A by Apple Tree Partners (ATP), a leader in life sciences venture capital, with $2.65 billion in committed capital.

POSITION SUMMARY

Marlinspike is seeking an experienced cell and molecular biologist to join a dynamic drug discovery team focused on developing small molecule inhibitors for genomically-defined cancer patient populations. We are looking for someone with experience studying the cellular functions and mechanisms of protein complexes involved in RNA transcription, DNA repair and/or related processes. In this role, you will play a critical role in advancing the company’s mission to develop innovative splicing modulators for the treatment of cancer. You will also define small molecule mechanism of action and support biomarker and translational strategies with line of sight to the clinic.

The successful candidate will have: Expertise in the growth and engineering of human cancer cell models; deep experience with experimental design, small molecule screening, and data interpretation for quantitative assessment of on-target inhibitor potency, including anti-proliferation assays, apoptosis assays, measurement of RNA transcript levels (e.g., qRT-PCR and NanoString), and cellular target engagement assays (e.g., thermal shift assays and nanoBRET).

This individual will become part of an interdisciplinary team of biologists, biochemists and chemists developing targeted small molecule modulators of RNA splicing. This laboratory-based role will require creativity in applying molecular, cellular, and biochemical methods to discover selective small molecule inhibitors and define mechanism of action. Prior industry or academic experience in transcriptional biology, cancer biology, immunology, and drug screening will be an advantage. Strong work ethic and meticulous record keeping are essential.

KEY RESPONSIBILITIES

• Culture and CRISPR engineer disease-relevant cancer cell models for knock-down studies and screening
• Apply transcriptomic, genomic and epigenomic assays to understand cancer cell dependencies
• Develop and maintain internal screening capabilities for quantitative analysis of on-target inhibitor activity in cells (Proliferation, target engagement, RNA modulation)
• Conduct small molecule inhibitor studies to determine drug-target interactions and MOA
• Collaborate within a cross-functional team to integrate biology, biochemistry and chemistry efforts to develop novel small molecule drug candidates
• Discover and develop patient selection and PD markers of on-target activity
• Present research results in internal and external scientific meetings

SUCCESS FACTORS

• Exceptional interpersonal skills and ability to work effectively with cross-functional teams and across partner research organizations
• Creativity and rigor in experimental design and execution
• Independent thinking, experimentation and analysis
• Strong communication skills and ability to share ideas and information with colleagues at multiple levels of the organization

JOB REQUIREMENTS

• Ph.D. in Molecular Biology or related field with 3-5 years of experience in drug discovery and RNA biology
• Proven core competency in cellular and molecular biology techniques, including methods to characterize protein-ligand interactions in cells
• Demonstrated capabilities in quantitative analysis of molecular and cellular biology data
• Ability to design, execute and analyze experiments to elucidate small molecule effects on protein complexes and protein degradation/turnover in cells
• Experience with immunology or immune-oncology is a plus
• Experience in team leadership and/or direct mentorship of scientists

Candidates who are keen experimentalists, independent thinkers, and enthusiastic team players that have a passion for drug discovery are encouraged to apply.

Marlinspike Therapeutics is an equal opportunity employer. We thrive on diversity and collaboration.