Biology subjects

Wong, M. K.

Publications and source records attributed to Wong, M. K..

4 recordsLinked to original sources

bioRxiv2026

High-throughput, organ-scale 3D tubule tracking using TubuleMAP

Advances in tissue clearing and lightsheet microscopy enable mesoscale imaging of intact and convoluted tubular networks, yet analytical tools to map tubule continuity and assess injury patterns within and across tubules are limited. Here, we introduce TubuleMAP, a semi-automated pipeline for 3D tubule tracking and reconstruction that adapts to various morphological and staining patterns, leverages parallel processing of terabyte-scale data for large-scale analysis of tubular networks, and uses a napari interface for human oversight. Using TubuleMAP, we reconstruct 1,000 intact mouse nephrons in [~]1-millimeter-thick kidney slab with [~]400-fold higher throughput and <1% human effort compared to prior approaches. These reconstructions enable analysis of mesoscale nephron organization, quantitative profiling of pathologic morphologies, whole-nephron cytometry, and identification of rare morphologies at unprecedented scales. We demonstrate generalizability by reconstructing all seminiferous tubules in a mouse testis within a day. TubuleMAP is released as an open-source Python package.

bioengineering↗

bioRxiv2024

Nanoscale Optical Imaging, Reconstruction, and Spatial Analysis of Whole Mouse Glomeruli

Renal glomeruli have traditionally been studied by micrometer-scale optical microscopy to interrogate overall physiology or molecular distributions and by nanoscale electron microscopy to interrogate the ultrastructure of thin sections. While these approaches are powerful, they have been limited in their ability to obtain detailed views of the glomeruli as holistic 3D functional units. To fill this knowledge gap, we have developed a novel pipeline for imaging, reconstructing, and analyzing whole mouse glomeruli at 100 nm resolution using super-resolution fluorescence microscopy. This pipeline integrates both manual and machine learning approaches to annotate and analyze glomerular structures. Using this method, we created 18 detailed glomerulus models, from a range of healthy, aged, and model diseased mice, that outline all major structures and cell types. These models have been made publicly accessible in an online repository, providing a valuable resource for further studies. Our results also uncovered a diverse set of novel phenotypes including nuclear enlargement in all glomerular cell types in aging and disease, as well as an aging-related pattern of regional thickening of the Bowmans capsule basement membrane near the tubular-glomerular junction.

physiology↗

bioRxiv2020

Conserved prolines in the coiled coil-OB domain linkers of proteasomal ATPases facilitate eukaryotic proteasome base assembly

The proteasome is a large protease complex that degrades both misfolded and regulatory proteins. In eukaryotes, the 26S proteasome contains six different AAA+ ATPase subunits, Rpt1-Rpt6, which form a hexameric ring as part of the base subcomplex that drives unfolding and translocation of substrates into the proteasome core. Archaeal proteasomes contain only a single type of ATPase subunit, the proteasome-activating nucleotidase (PAN), which forms a trimer-of-dimers and is homologous to the eukaryotic Rpt subunits. A key PAN proline residue (P91) forms cis and trans peptide bonds in successive subunits around the ring, allowing efficient dimerization through upstream coiled coils. The importance of the equivalent Rpt prolines in eukaryotic proteasome assembly was unknown. We show an equivalent proline is strictly conserved in Rpt3 (in S. cerevisiae, P93) and Rpt5 (P76), well conserved in Rpt2 (P103), and loosely conserved in Rpt1 (P96) in deeply divergent eukaryotes, but in no case is its mutation strongly deleterious to yeast growth. However, the rpt2-P103A, rpt3-P93A, and rpt5-P76A mutations all cause synthetic defects with specific base assembly chaperone deletions. The Rpt5-P76A mutation decreases the levels of the protein and induces a mild proteasome assembly defect. The yeast rpt2-P103A rpt5-P76A double mutant has strong growth defects attributable to defects in proteasome base formation. Several Rpt subunits in this mutant form aggregates that are cleared, at least in part, by the Hsp42-mediated protein quality control (PQC) machinery. We propose that the conserved Rpt linker prolines promote efficient 26S proteasome base assembly by facilitating specific ATPase heterodimerization.

biochemistry↗

bioRxiv2019

The cryptic impacts of invasion: functional homogenization of tropical ant communities by invasive fire ants

Invasive insects represent major threats to ecosystems worldwide. Yet their effects on the functional dimension of biodiversity, measured as the diversity and distribution of traits, are overlooked. Such measures often determine the resilience of ecological communities and the ecosystem processes they modulate. The fire ant Solenopsis invicta is a highly problematic invasive species occurring on five continents. Its impacts on the taxonomic diversity of native ant communities have been studied but its impacts on their functional diversity are unknown. Comparing invaded and uninvaded plots in tropical grasslands of Hong Kong, we investigated how the presence of S. invicta affects the diversity and distribution of ant species and traits within and across communities, the functional identities of communities, and functionally unique species. We calculated the functional diversity of individual species, including the trait variation from intraspecific polymorphisms, and scaled up these values to calculate functional diversity at the community level. Invasion had only limited effects on species richness and functional richness, which were 13% and 8.5% lower in invaded communities respectively. In contrast, invasion had pronounced effects on taxonomic and functional composition due to turnover in species and trait values. Furthermore, invaded communities were functionally more homogeneous, displaying 23% less turnover and 56% more redundancy than uninvaded communities, as well as greater clustering and lower divergence in trait values. Invaded communities had fewer functionally-unique individuals and were characterized by ant species with narrower heads and bodies and shorter mandibles. Our results suggest that studies based only on taxonomic measures of diversity or indices describing trait variety risk underestimating the full ramifications of invasions. Investigating the diversity and distributions of traits at species, community and landscape levels can reveal the cryptic impacts of alien species which, despite causing little taxonomic change, may substantially modify the structure and functioning of ecological communities.

ecology↗