Scientist I / Senior Research Associate (Contract)

About Fulcrum

Fulcrum Neuroscience is a biotech startup developing new therapeutic approaches to Alzheimer’s disease and other neurodegenerative conditions. At the heart of Fulcrum’s approach is a unique computational platform: the Brain Health and Neurodegeneration world model, reconciling over 1,800 literature and data sources, and an underlying AI-enabled, digital twin computational engine. This platform enables Fulcrum scientists to explore target and therapeutic alternatives, identify biomarker patterns, and design lab and clinical experiments.

Fulcrum recently established a new laboratory in South San Francisco, CA, and is building a team to develop and execute an ambitious research plan for the development of new classes of Alzheimer’s therapeutics. Experimental work and computational work proceed in tandem, each informing the other.

The Role

Reporting to the VP, Biology, you will execute the company's experimental plan in iPSC-based and primary cellular models, working closely with the scientific co-founders who direct the research agenda. The work spans three integrated cell systems:

• Primary human astrocytes — pharmacological lipid loading, ApoE genotype-stratified challenge studies, and functional cellular readouts of receptor signaling and metabolic output.
• iPSC-derived astrocyte–neuron co-culture — isogenic ApoE3/E4 model systems with functional, imaging, and mass spectrometry–based biomarker readouts.
• iPSC-derived microglia — induction of disease-relevant lipid-handling states, evaluation of candidate therapeutic compounds, and assays of intracellular lipid trafficking and clearance.

You will own specific experimental arms, troubleshoot and optimize protocols, present data in internal review meetings, and contribute as an author on publications emerging from the program. You may also be asked to participate in scientific work on the computational side, in support of Fulcrum’s efforts and collaborations. Scope and ownership grow with demonstrated capability.

This is a fully on-site role in South San Francisco — cell culture work requires flexibility to come in as the cells and experiments demand, including some evenings, weekends, and holidays.

Qualifications

Required

• PhD in cell biology, neuroscience, biochemistry, or related field with hands-on iPSC experience; OR MS with 5+ years industry bench experience running iPSC-based assays.
• Demonstrated competence in iPSC maintenance and differentiation in at least one glial or neuronal lineage.
  Fluency with confocal and/or high-content imaging, including quantitative analysis of cellular phenotypes.
• Comfort with standard molecular and cell biology methods (qPCR, Western blot, ELISA, flow cytometry, siRNA transfection).
• Bay Area-based or willing to relocate within 60 days; able to work on-site in South San Francisco.

Highly Desired

• Experience with iPSC microglia, or with co-culture and tri-culture systems.
• Interest in lipid biology, cholesterol homeostasis, or neuroimmune mechanisms in neurodegeneration.
• Receptor signaling assay experience.
• Familiarity with mass spectrometry sample preparation or lipidomics data interpretation.

What We Offer

• Integration with the hypothesis-generation layer of the company. Fulcrum's experimental program is driven by AI-augmented multi-omic biomarker discovery and systems-level target identification. You will see how computational target ID translates to bench experiments and work directly with the people doing that work, rather than receiving targets from a black box.
• A clear growth path. Demonstrated ownership translates into Scientist II / Senior Scientist roles as the program and team scale.
• Authorship on publications emerging from your experimental contributions.
• Meaningful early-stage equity and contract rate commensurate with experience.

This is a contract role with the potential for transition to an employee role in the future. Engagement structure (full-time, part-time, or transition-from-postdoc) is open to discussion with the right candidate.

Direct applicants only, please. We are not working with staffing agencies or third-party recruiters for this contract opportunity and are not accepting agency-submitted candidates.