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Biology subjects

Wang, S.-W.

Publications and source records attributed to Wang, S.-W..

3 recordsLinked to original sources

Emergent oscillations in dense adaptive cell populations

Collective oscillations of cells in a population appear under diverse biological contexts. Here, we establish a set of common principles by categorising the response of individual cells against a time-varying signal. A positive intracellular signal relay of sufficient gain from participating cells is required to sustain the oscillations, together with phase matching. The two conditions yield quantitative predictions for the onset cell density and frequency in terms of measured single-cell and signal response functions. Through mathematical constructions, we show that cells that adapt to a constant stimulus fulfil the phase requirement by developing a leading phase in an active frequency window that enables cell-to-signal energy flow. Analysis of dynamical quorum sensing in several cellular systems with increasing biological complexity reaffirms the pivotal role of adaptation in powering oscillations in an otherwise dissipative cell-to-cell communication channel. The physical conditions identified also apply to synthetic oscillatory systems.

biophysics

Revealing evolutionary constraints on proteins through sequence analysis

Alignments of large numbers of protein sequences have revealed \"sectors\" of collectively coevolving amino acids in several protein families. Here, we show that selection acting on any relevant physical property of a protein, e.g. the elastic energy of an important conformational change, can give rise to such a sector. We demonstrate that the main signature of these physical sectors lies in the smalleigenvalue modes of the covariance matrix of the selected sequences. This simple, generic model leads us to propose a principled method to identify sectors, along with the magnitudes of mutational effects, from sequence data.

biophysics

Engineered resistance to Zika virus in transgenic Ae. aegypti expressing a polycistronic cluster of synthetic miRNAs

Recent Zika virus (ZIKV) outbreaks have highlighted the necessity for development of novel vector control strategies to combat arboviral transmission, including genetic versions of the sterile insect technique, artificial infection with Wolbachia to reduce population size and/or vectoring competency, and gene drive based methods. Here, we describe the development of mosquitoes synthetically engineered to impede vector competence to ZIKV. We demonstrate that a polycistronic cluster of engineered microRNAs (miRNAs) targeting ZIKV is expressed and fully processed following a blood meal in Ae. aegypti, ensuring the formation of mature synthetic miRNAs in the midgut where ZIKV resides in the early stages of infection. Critically, we demonstrate that engineered Ae. aegypti mosquitoes harboring the anti-ZIKV transgene have significantly reduced viral infection, dissemination, and transmission rates of ZIKV. Taken together, these compelling results provide a promising path forward for development of effective genetic-based ZIKV control strategies, which could potentially be extended to curtail other arboviruses.\n\nOne Sentence SummaryHere we describe the generation of Ae. aegypti mosquitoes that are engineered to confer reduced vector competence to Zika virus (ZIKV) and we discuss how such engineering approach can be used to combat the major health burden of ZIKV and potentially other arboviruses in the future.

synthetic biology