Catalytic mechanisms, regulation, and anti-fibrotic roles of the TMEM2 cell surface hyaluronidase
About This Grant
PROJECT SUMMARY Hyaluronan (HA), a member of the glycosaminoglycan family, is one of the most abundant components of extracellular matrices. HA is a huge polysaccharide — a single linear HA polymer often exceeds 25,000 disaccharide units in length (~107 Da) and occupies the volume of a 300 nm diameter sphere. These unique biochemical and biophysical properties are accompanied by another unique biological feature of HA —an extremely rapid turnover. For instance, the metabolic half-life of HA in skin is only 1–1.5 days. This rapid turnover of HA emphasizes the particular importance of HA degradation in regulating systemic HA homeostasis and the biological effects of HA on cells. The prevailing model of HA catabolism stipulates that high-molecular weight HA in the extracellular space is first partially degraded into smaller HA fragments in the vicinity of the plasma membrane prior to internalization and ultimate degradation of the fragments in lysosomes. Accordingly, the existence of a hyaluronidase(s) that acts on the cell surface has been postulated. However, the identity of such a hyaluronidase(s) has long been elusive. In this context, we identified TMEM2, a previously uncharacterized transmembrane protein, as the sought-after cell surface hyaluronidase. Our subsequent studies have confirmed TMEM2's identity as a bona fide HA-degrading enzyme, and further demonstrated its functional significance in systemic HA catabolism, embryonic development, and cell adhesion and migration. Notably, the cellular and in vivo phenotypes caused by TMEM2 inactivation are much more striking than the phenotypes caused by inactivation of previously-known hyaluronidases. Moreover, an increasing number of genomic and transcriptomic studies implicate the TMEM2 gene in several human diseases. These observations indicate that mechanistic models of HA metabolism that do not incorporate TMEM2 are incomplete, and suggest that dysfunction of HA catabolism may have much more significant relevance to human diseases than previously thought. To fill this void in our understanding of the physiological and pathophysiological significance of HA catabolism, this project will comprehensively characterize the enzymology, three-dimensional structure, and cellular regulation of this novel hyaluronidase. Building on extensive published and preliminary data, we will determine the structural basis of TMEM2 catalytic function and elucidate cellular mechanisms that regulate TMEM2 function. The insights gained from this project are expected to uncover fundamental mechanisms governing HA metabolism and illuminate its pathophysiological significance in human disease.
Grant Summary
Catalytic mechanisms, regulation, and anti-fibrotic roles of the TMEM2 cell surface hyaluronidase is a NIGMS - National Institute of General Medical Sciences grant providing up to $1.7M for university, nonprofit, healthcare org. Applications are due 2030-03-31 (open). Check eligibility and apply with FindGrants.
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Up to $1.7M
2030-03-31
- 1Confirm your organization is eligible for Catalytic mechanisms, regulation, and anti-fibrotic roles of the TMEM2 cell surface hyaluronidase from NIGMS - National Institute of General Medical Sciences, checking organization type, location, and any population or project requirements.
- 2Gather the required documents and information, including your organization details, project plan, and budget figures.
- 3Draft your application narrative and budget addressing the funder's priorities and review criteria. FindGrants can draft each section for you to review and edit.
- 4Review every section against the requirements checklist, then export a submission-ready application pack and submit it to NIGMS - National Institute of General Medical Sciences before the deadline.
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Catalytic mechanisms, regulation, and anti-fibrotic roles of the TMEM2 cell surface hyaluronidase: Frequently Asked Questions
Who is eligible for the Catalytic mechanisms, regulation, and anti-fibrotic roles of the TMEM2 cell surface hyaluronidase?
Catalytic mechanisms, regulation, and anti-fibrotic roles of the TMEM2 cell surface hyaluronidase is offered by NIGMS - National Institute of General Medical Sciences and is generally open to university, nonprofit, healthcare org. It is open to organizations nationwide unless the funder specifies otherwise. Review the specific eligibility terms before applying, since funders set their own requirements around organization type, location, and the population or project being served.
How much funding does the Catalytic mechanisms, regulation, and anti-fibrotic roles of the TMEM2 cell surface hyaluronidase provide?
Catalytic mechanisms, regulation, and anti-fibrotic roles of the TMEM2 cell surface hyaluronidase provides up to $1.7M per award from NIGMS - National Institute of General Medical Sciences. Actual award sizes depend on the scope of your project, available program funds, and the number of applicants, so build a budget that reflects realistic, allowable costs rather than the maximum figure.
When is the Catalytic mechanisms, regulation, and anti-fibrotic roles of the TMEM2 cell surface hyaluronidase deadline?
Applications for Catalytic mechanisms, regulation, and anti-fibrotic roles of the TMEM2 cell surface hyaluronidase are due 2030-03-31 (open). Because deadlines can change, verify the date with the funder, NIGMS - National Institute of General Medical Sciences, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the Catalytic mechanisms, regulation, and anti-fibrotic roles of the TMEM2 cell surface hyaluronidase?
To apply for Catalytic mechanisms, regulation, and anti-fibrotic roles of the TMEM2 cell surface hyaluronidase, confirm your eligibility, gather the required documents, and prepare a narrative and budget that address the funder's priorities. FindGrants guides you step by step and can draft each section, then exports a submission-ready application pack for this grant from NIGMS - National Institute of General Medical Sciences.