The role Akirin and Pannier interactions during myogenesis
Project Number5R16GM145448-03
Contact PI/Project LeaderNOWAK, SCOTT JAMES
Awardee OrganizationKENNESAW STATE UNIVERSITY
Description
Abstract Text
Project Summary
Myogenic defects, which includes congenital heart malformations as well as congenital muscular dystrophies
are the most prevalent classes of birth defects in the human population, with an incident rate as high as 10 in
1000 live births. A significant number of these cases are termed sporadic, which are largely the result of
interactions between a number of independent genetic loci and alleles. To aid in our understanding of the
polygenic nature of congenital myogenic defects, it remains imperative to continue to identify new gene
regulatory partners that may play a role in the process of embryonic heart and skeletal muscle patterning. Our
laboratory has recently identified a cofactor, Akirin, that is responsible for interfacing transcription factor activity
with chromatin remodeling machinery to facilitate gene expression during a variety of skeletal myogenic and
cardiogenic processes. To date, the number of developmentally critical transcription factors known to interact
with Akirin remains frustratingly low, despite the myriad developmental processes known to require Akirin for
proper function. Excitingly, our preliminary data suggests that Akirin likely regulates insect embryonic heart
development and/or skeletal muscle development through interactions with the GATA-family member Pannier,
a zinc finger transcription factor identified as key for embryonic segmentation as well as cardiomyoblast
specification.
This project therefore involves simultaneous pursuit of two related specific aims: 1) Using a combination of
genetic, biochemical, and live imaging techniques, will confirm the importance of Akirin/Pannier interactions
during development, and 2) We will deploy a focused candidate screen for Akirin interacting loci, based on a
small number (25) of predicted Akirin interactors. This work will provide key data for understanding the role of
Akirin in the process of skeletal muscle and heart formation, and generate a further list of Akirin-interacting locian
Akirin interactome- that will shed light on other myogenic regulatory nodes that require Akirin.
Critically, in keeping with the goals of the Su RE award mechanism, this project will support the research
activities of the Pl, whose previously NIH-supported laboratory has an established track record of recruiting
talented undergraduate researchers from diverse backgrounds. Members of the Nowak Laboratory gain
hands-on experience in a wide variety of molecular, genetic, histological, microscopic, and biochemical
techniques, and are actively involved in not only project conception and execution, but also dissemination of
results and findings through conference presentations and authorships on peer-reviewed manuscripts.
Public Health Relevance Statement
Project Narrative
Heart and/or skeletal muscle defects in newborn infants remain the most prevalent form of
human birth defects, yet the exact genes and genetic processes that can either positively or
negatively affect muscle development remain unknown. Studies on Akirin, a nuclear protein
that is found in both fruit flies and humans, have indicated that Akirin works with a novel class
of regulators to facilitate heart and skeletal muscle development By studying the role of Akirin
during this process in fruit fly embryos, we will learn how this protein likely functions in
vertebrates, such as mammals, during heart formation.
No Sub Projects information available for 5R16GM145448-03
Publications
Publications are associated with projects, but cannot be identified with any particular year of the project or fiscal year of funding. This is due to the continuous and cumulative nature of knowledge generation across the life of a project and the sometimes long and variable publishing timeline. Similarly, for multi-component projects, publications are associated with the parent core project and not with individual sub-projects.
No Publications available for 5R16GM145448-03
Patents
No Patents information available for 5R16GM145448-03
Outcomes
The Project Outcomes shown here are displayed verbatim as submitted by the Principal Investigator (PI) for this award. Any opinions, findings, and conclusions or recommendations expressed are those of the PI and do not necessarily reflect the views of the National Institutes of Health. NIH has not endorsed the content below.
No Outcomes available for 5R16GM145448-03
Clinical Studies
No Clinical Studies information available for 5R16GM145448-03
News and More
Related News Releases
No news release information available for 5R16GM145448-03
History
No Historical information available for 5R16GM145448-03
Similar Projects
No Similar Projects information available for 5R16GM145448-03