Honors & Awards
Lavidge and McKinley Interdisciplinary Fellow, BioX (2017-2020)
'Chromatic' neuronal jamming in a primitive brain
View details for DOI 10.1038/s41567-020-0809-9
Mechanically resolved imaging of bacteria using expansion microscopy.
2019; 17 (10): e3000268
Imaging dense and diverse microbial communities has broad applications in basic microbiology and medicine, but remains a grand challenge due to the fact that many species adopt similar morphologies. While prior studies have relied on techniques involving spectral labeling, we have developed an expansion microscopy method (muExM) in which bacterial cells are physically expanded prior to imaging. We find that expansion patterns depend on the structural and mechanical properties of the cell wall, which vary across species and conditions. We use this phenomenon as a quantitative and sensitive phenotypic imaging contrast orthogonal to spectral separation to resolve bacterial cells of different species or in distinct physiological states. Focusing on host-microbe interactions that are difficult to quantify through fluorescence alone, we demonstrate the ability of muExM to distinguish species through an in vitro defined community of human gut commensals and in vivo imaging of a model gut microbiota, and to sensitively detect cell-envelope damage caused by antibiotics or previously unrecognized cell-to-cell phenotypic heterogeneity among pathogenic bacteria as they infect macrophages.
View details for DOI 10.1371/journal.pbio.3000268
View details for PubMedID 31622337
Locked Expansion Microscopy to in Situ Analyze Microbial Communities
CELL PRESS. 2018: 532A
View details for Web of Science ID 000430563200415
- Nanoengineered Osteoinductive and Elastomeric Scaffolds for Bone Tissue Engineering ACS BIOMATERIALS SCIENCE & ENGINEERING 2017; 3 (4): 590–600
Maintenance of neural progenitor cell stemness in 3D hydrogels requires matrix remodelling.
2017; 16 (12): 1233–42
Neural progenitor cell (NPC) culture within three-dimensional (3D) hydrogels is an attractive strategy for expanding a therapeutically relevant number of stem cells. However, relatively little is known about how 3D material properties such as stiffness and degradability affect the maintenance of NPC stemness in the absence of differentiation factors. Over a physiologically relevant range of stiffness from ∼0.5 to 50 kPa, stemness maintenance did not correlate with initial hydrogel stiffness. In contrast, hydrogel degradation was both correlated with, and necessary for, maintenance of NPC stemness. This requirement for degradation was independent of cytoskeletal tension generation and presentation of engineered adhesive ligands, instead relying on matrix remodelling to facilitate cadherin-mediated cell-cell contact and promote β-catenin signalling. In two additional hydrogel systems, permitting NPC-mediated matrix remodelling proved to be a generalizable strategy for stemness maintenance in 3D. Our findings have identified matrix remodelling, in the absence of cytoskeletal tension generation, as a previously unknown strategy to maintain stemness in 3D.
View details for PubMedID 29115291