Department of Food Science and Human Nutrition
Iowa State University
Research Interests
Since the initial identification of microRNAs (miRNAs) as a class of molecules regulating gene expresion, significant roles for miRNAs in development and disease have emerged. Thousands of miRNAs have been identified in various species, and it is estimated that collectively miRNAs have the potential to target nearly two thirds of all mRNAs. Despite rapid progress in understanding the molecular mechanisms underlying miRNA biogenesis and mechanisms of action, the biological functions of most miRNAs remain elusive.
The McNeill lab is working to define functions of non-coding regulatory RNAs in development and maintenance of complex tissues to understand how miRNAs contribute to normal development and disease. We are using techniques we helped to develop and validate for studying microRNA function in vivo in a tissue-specific and temporal-specific way. To best answer our questions, our studies will utilize a multi-disciplinary experimental platform combining genetic approaches with RNA biochemistry, molecular biology, bioinformatics, fluorescence imaging, optogenetics and genome engineering.
​
Projects
​
The Role of miRNA in the formation and maintenance of neuronal connections
The extensive complexity of neuronal connections elicits questions about how the genome encodes for the great cellular diversity and morphological flexibility required in nervous system function. Neuronal circuits require a highly regulated, yet dynamic, mechanism to determine the strength and localization of synaptic connections, ultimately forming and maintaining the basis of nervous system function including movement, learning and memory.
​
Several individual miRNAs have been demonstrated to function in synaptic development and maintenance during aging. However the breadth and tissue selectivity of miRNA function in synaptogenesis is largely unknown. To examine this, a comprehensive loss-of-function tool to screen for the mophological implications of miRNA loss was developed and used to identify a substantial role with close to 16% of conserved microRNAs acting in synaptogenesis. Moving forward, our lab is examining the tissue-specific requirements for these identified miRNAs as well as their gene target networks and possible role in synaptic plasticity in response to neuronal stimulation.
The Role of miRNA in maintaining heart muscle during aging
Aging is one of the most significant risk factors for the development of cardiovascular disease. As human life expectancy increases, a rapidly growing percentage of the population is over the age of 65. Cardiovascular disease is the leading cause of death in this age group accounting for 40% of all deaths. The costs associated with treatment for this disease continue to increase. Understanding the complex process of heart tissue maintenance in aging is vital to addressing this risk factor, reducing costs and, most importantly, extending life. Identification of key genetic players and their regulation specific to tissue maintenance will hold therapeutic potential for the treatment of cardiac dysfunction.
microRNAs (miRNAs) have emerged as ideal candidates for regulating the genes involved in growth and maintenance of heart tissue, but our knowledge of individual miRNA function in the heart is limited. This project focuses on the role of highly human-conserved miRNAs which have been previously identified to play a significant role in muscle tissue maintenance (Fulga and McNeill et al., 2015). The project focuses on examining the conservation of miRNA function in heart tissue, the temporal requirement for these microRNAs, and identification of the conserved gene networks functioning downstream of the individual microRNAs.