Homework

Weekly homework submissions:

• Week 1 HW: Principles and Practices
• Week 2 HW: DNA read, write and edit
• Week 3 HW: Lab Automation

Biological Engineering Application: A Functional Expression Platform for Classifying Variants of Uncertain Significance (VUS) in Cystic Fibrosis

My proposal is to develop a standardized, accessible platform for the functional expression and characterization of variants in the CFTR gene, specifically focusing on Variants of Uncertain Significance (VUS) identified in underrepresented populations in Ecuador.

The core application integrates three components: rapid synthesis and cloning of CFTR gene constructs containing locally identified VUS; expression of these constructs in relevant, standardized human cell lines (e.g., immortalized bronchial epithelial cells); and a multiparametric, high-content functional assay suite.

This suite would automatically measure key parameters: subcellular localization via microscopy, protein processing and maturation via western blot, ion channel function via fluorescence-based halide assays, and response to CFTR modulator drugs.

The motivation for this tool is to address a critical equity gap in genomic medicine. Global genetic databases like ClinVar are heavily biased toward populations of European descent. Consequently, variants identified in mestizo, Indigenous, or Afro-descendant populations in Ecuador and similar regions are often classified as VUS due to a lack of functional and phenotypic data.

This has direct, harmful clinical consequences: it leads to ambiguous diagnoses for patients and families, restricts access to modern, highly effective modulator therapies that are approved for specific variants, and perpetuates health disparities.

This platform aims to functionalize genomics by converting raw genetic data into actionable clinical knowledge, deliberately prioritizing variants from historically underserved populations to ensure that precision medicine benefits extend globally.