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Boye, S.

Publications and source records attributed to Boye, S..

2 recordsLinked to original sources

Theory bridging cell polarities with development of robust complex morphologies

Despite continual renewal and damages, a multicellular organism is able to maintain its complex morphology. How is this stability compatible with the complexity and diversity of living forms? Looking for answers at protein level may be limiting as diverging protein sequences can result in similar morphologies. Inspired by the progressive role of apical-basal and planar cell polarity in development, we propose that stability, complexity, and diversity are emergent properties in populations of proliferating polarized cells. We support our hypothesis by a theoretical approach, developed to effectively capture both types of polar cell adhesions. When applied to specific cases of development gastrulation and the origins of folds and tubes our theoretical tool suggests experimentally testable predictions pointing to the strength of polar adhesion, restricted directions of cell polarities, and the rate of cell proliferation to be major determinants of morphological diversity and stability.

biophysics

A drug-tunable gene therapy for broad-spectrum protection against retinal degeneration

Retinal degenerations are a large cluster of diseases characterized by the irreversible loss of light-sensitive photoreceptors that impairs the vision of 9.1 million people in the US. An attractive treatment option is to use gene therapy to deliver broad-spectrum neuroprotective factors. However, this approach has had limited clinical translation because of the inability to control transgene expression. To address this problem, we generated an adeno-associated virus vector named RPF2 that was engineered to express domains of leukemia inhibitory factor fused to the destabilization domain of bacterial dihydrofolate reductase. Fusion proteins containing the destabilization domain are degraded in mammalian cells but can be stabilized with the binding of the drug trimethoprim. Our data show that expression levels of RPF2 are tightly regulated by the dose of trimethoprim, and can be reversed by trimethoprim withdrawal. We further show that stabilized RPF2 can protect photoreceptors and prevent blindness in treated mice.

bioengineering