µMacro Architectures in Biology
Purnati Khuntia, Ph.D.
Rowland Institute at Harvard
Our Research
Pseudostratified epithelium, unlike pseudoscience, is of great interest to researchers across fields.
The pseudostratified epithelium (PSE) is a specific subtype of epithelium with unique structural characteristics. Although a monolayer, it appears stratified due to multilayered nuclear positioning in the cells, creating the "pseudo" stratified appearance. Pseudostratified epithelia are a crucial part of organ development across invertebrates and vertebrates; as well as adult proliferating tissues due to their high proliferation rate. Despite the prevalence of PSE in organ development across invertebrates and vertebrates, the function of the pseudostratified architecture in epithelial systems during morphogenesis remains largely unanswered. We ask the question, Why Psuedostratification?!
We believe the answer to the question we pose lies in the physical properties of PSE at the cellular and intracellular levels. The relationship between cell packing and nuclear layering is one of the key physical factors in PSE. By exploiting this physical property, pseudostratification could act as a brilliant cell storage mechanism. At the cellular level, this is likely achieved by multilayered nuclear positioning in the epithelium. With this perspective, we plan to understand how the pseudostratified architecture contributes to the three fundamental behaviors of the tissue: i) High Proliferation rate, ii) Tissue height variation across PSE, and iii) Interkinetic Nuclear Migration (IKNM).
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We use pseudostratified tissues from various organisms (Fruit fly, Moth, Mouse, mESC derived Retinal organoids) to study the role of Nuclear positioning in the PSE architecture. The primary objectives we want to pursue are;
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Investigate the establishment of Pseudoostratified epithelium (PSE) architecture in organoids and tissues using advanced fluorescent and lattice light sheet 3D-time lapse imaging to monitor cell and Nuclear dynamics.
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Manipulate local nuclear packing on PSE architecture using a custom-built optogenetic actin polymerization tool. And examine how altering nuclear position in cells affects cell packing, tissue curvature, and folding.
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Exploiting micropatterned culturing methods, explore the role of PSE architecture in regulating tissue thickness. Investigate how confinement conditions influence PSE height and architecture using stretchable confinements like Polydimethylsiloxane (PDMS) and hydraulic pressure adjustments in organoids and tissues.
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Fundamental discoveries often made in labs with model organisms can also be found in Nature in the wild. Therefore, we plan to examine our primary interest in unconventional model organisms (insect species, plants, etc). We look forward to new collaborations!