FY21 Faculty Seed Grant Winners

Congratulations to our FY21 Seed Grant Award winners!

Each of the following novel research projects has been granted $25,000 to support innovative research in the field of mechanobiology.

A Novel Mechanochemical Bioreactor Platform for Synovial Joint Therapeutic Screening
Co-PIs Michael Albro, Mark Grinstaff, and Brian Snyder
Project Summary:
Osteoarthritis (OA) is a chronic, debilitating, synovial joint condition that progressively degrades articular cartilage, leading to pain and disability. Currently there exists no therapy to inhibit the progression of OA.  In the current project, we aim to develop a novel analytical platform in order to perform high throughput testing of OA therapy candidates.  The platform implements a bioreactor that recreates the mechanical and chemical environment of the synovial joint on live cartilage specimens that are explanted from animal or human donor tissues.  Further, it implements a novel, light-based technology to achieve the first-ever repeated-measure monitoring of tissue degeneration or healing in response to therapeutics.  Overall, this platform will be able to identify therapeutic drug candidates that can subsequently be used in expanded in vivo animal-based OA treatment studies.

Impaired Mechanotransduction in Connective Tissue Disease
Co-PIs Matthew Layne, Joyce Wong, Michael Smith, and Katherine Zhang
Project Summary:
Heritable connective tissue disorders are caused by genetic mutations that result in structurally disorganized and weak tissues.  There are currently no effective therapies to treat the tissue fragility, impaired wound healing, and vascular disruptions in these diseases resulting in significant pain, suffering, and in some cases, death.  Collagens and collagen-regulatory proteins are secreted by cells and form a so-called extracellular matrix (ECM) that is essential for tissue integrity.  Humans with mutations in the AEBP1 gene, which encodes the collagen regulatory protein aortic carboxypeptidase-like protein (ACLP), have weak connective tissues resulting in joint hypermobility, vascular complications, and defective wound healing.  We postulate that ACLP contributes to connective tissue mechanical strength by instructing cells to produce ECM proteins and also by regulating collagen assembly.  These studies will have broad implications for understanding the mechanisms of connective tissue disorders and will provide the foundation for future interdisciplinary research projects.

Multiscale approaches for engineering and understanding mechanical communication between cells
Co-PIs John Ngo and Joseph Larkin
Project Summary:
Similar to how humans use touch in order to feel objects and sense their surroundings, cells, tissues, and bacteria are also able to sense the mechanical features of their environments.  Although ability has been link to numerous biological processes—including cancer, infection, and stem cell differentiation—the ways by which cells detect and respond to mechanical forces, and the set of genes that encode these abilities, remain mysterious.  In this research, we will develop new tools to study how various organisms sense and interpret mechanical signals, with the long-term goal of identifying new strategies and drug targets to treat human diseases and bacterial infections.

Mechanical signatures of cell-specific transcriptomics of the lung
Co-PIs Hadi Nia and Bela Suki
Project Summary:
The lung is one of the most active organs, and there is abundant evidence on how the mechanical properties of the lung affect its function and dysfunction in health and disease.  However, the causal links between the lung mechanics and genetics have not been studied systematically and comprehensively.  Here, by developing an experimental model system to keep a mouse lung viable outside the body, and coupling this system to multi-scale mathematical models, we will be able to control and monitor the key mechanical features of the lung.  Utilizing the developed tools and recent advances in sequencing technologies, we will provide the first atlas that describes how alterations in mechanical properties affect the gene expression of the diverse cellular constituents of the lung.  This atlas will be the cornerstone of future studies on how lung mechanics affects the progression of disease such as cancer, chronic obstructive pulmonary disease, and fibrosis.