Biology subjects

Locke, L.

Publications and source records attributed to Locke, L..

3 recordsLinked to original sources

bioRxiv2026

Engineering a 3D Lung Co-culture Platform to Model Epithelial-Fibroblast Interactions in Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease (ILD) characterized by progressive fibrosis, irreversible loss of lung elasticity, and chronic respiratory failure, with a mean survival of 3-5 years. The disease is believed to result from repeated alveolar epithelial injury that sustains transforming growth factor-beta (TGF-{beta}) signaling, driving fibroblast-to-myofibroblast differentiation and excessive collagen deposition. Although current IPF models--including animal studies, 2D cultures, and basic 3D systems--have enhanced understanding of disease mechanisms, they inadequately replicate epithelial-fibroblast interactions, extracellular matrix (ECM) remodeling, and epithelial barrier dysfunction. To address this limitation, we engineered a 3D lung co-culture model that simulates the physiological epithelial-fibroblast crosstalk and ECM remodeling characteristic of IPF. Our model embeds fibroblasts within a collagen-hyaluronic acid matrix overlaid with an epithelial monolayer cultured at an air-liquid interface. Basolateral TGF-{beta} exposure generated a profibrotic microenvironment that weakened epithelial barrier integrity and drove myofibroblast differentiation marked by elevated -SMA and vimentin. Elevated pro-inflammatory cytokine secretion and increased collagen disorganization further demonstrated active fibrogenesis. Together, these features show that our model captures key early events in IPF pathogenesis and offers a versatile platform for next-generation lung-on-a-chip studies in fibrotic disease.

bioengineering↗

bioRxiv2019

Visual-olfactory integration in the human disease vector mosquito, Aedes aegypti

Mosquitoes rely on the integration of multiple sensory cues, including olfactory, visual, and thermal stimuli, to detect, identify and locate their hosts [1-4]. Although we increasingly know more about the role of chemosensory behaviours in mediating mosquito-host interactions [1], the role of visual cues remains comparatively less studied [3], and how the combination of olfactory and visual information is integrated in the mosquito brain remains unknown. In the present study, we used a tethered-flight LED arena, which allowed for quantitative control over the stimuli, to show that CO2 exposure affects target-tracking responses, but not responses to large-field visual stimuli. In addition, we show that CO2 modulates behavioural responses to visual objects in a time-dependent manner. To gain insight into the neural basis of this olfactory and visual coupling, we conducted two-photon microscopy experiments in a new GCaMP6s-expressing mosquito line. Imaging revealed that the majority of ROIs in the lobula region of the optic lobe exhibited strong responses to small-field stimuli, but showed little response to a large-field stimulus. Approximately 20% of the neurons we imaged were modulated when an attractive odour preceded the visual stimulus; these same neurons also elicited a small response when the odour was presented alone. By contrast, imaging in the antennal lobe revealed no modulation when visual stimuli were presented before or after the olfactory stimulus. Together, our results are the first to reveal the dynamics of olfactory modulation in visually evoked behaviours of mosquitoes, and suggest that coupling between these sensory systems is asymmetrical and time-dependent.

neuroscience↗

bioRxiv2017

Modulation of host learning in Aedes aegypti mosquitoes

How mosquitoes determine which individuals to bite has important epidemiological consequences. This choice is not random; most mosquitoes specialize in one or a few vertebrate host species, and some individuals in a host population are preferred over others. Here we show that aversive olfactory learning contributes to mosquito preference both between and within host species. Combined electrophysiological and behavioural recordings from tethered flying mosquitoes demonstrated that these odours evoke changes in both behaviour and antennal lobe (AL) neuronal responses. Using electrophysiological and behavioural approaches, and CRISPR gene editing, we demonstrate that dopamine plays a critical role in aversive olfactory learning and modulating odour-evoked responses in AL neurons. Collectively, these results provide the first experimental evidence that olfactory learning in mosquitoes can play an epidemiological role.

neuroscience↗