Pedro Irazoqui, Ph.D. - US grants

DESCRIPTION (provided by applicant): The objective of this proposal is to develop and implement an educational experience that trains undergraduates to work on multidisciplinary teams to design solutions that address challenging, real-world biomedical problems at the interface of engineering and living systems. The proposed training employs pedagogical elements of modeling, scaffolding, coaching and fading to teach design principles. Active learning studio style courses that address responsible conduct in research are coupled with inquiry-based and design laboratories that are supported by faculty and clinical mentors within multidisciplinary and multicultural environments to transform the undergraduate students to practicing engineers well equipped with theoretical knowledge, creativity, ethical behavior, and strong problem solving skills. Within the proposed curriculum, the students fully experience the design process from need identification and idea generation through the iterative process to ultimately resolve the problem. Exposure to principles and successful examples of technology transfer, intellectual property, and commercialization prepare the students to take their design from the classroom to the clinical market. Recruitment activities will specifically target increasing the numbers of students from underrepresented racial, ethnic, and female groups as well as individuals with disabilities and those from disadvantaged backgrounds. Dissemination of findings and best practices will be through conference presentations, journal articles, and the internet. PUBLIC HEALTH RELEVANCE: Our proposed design training will prepare our undergraduate biomedical engineers to work on multidisciplinary teams and effectively generate and contribute to the solution of challenging, complex, real-world clinical and healthcare problems. These students will understand the product cycle, be able to recognize the potential for a new discovery or technology to address a current need, be creative and design solutions to clinical problems, and be prepared to translate their innovations into clinical solutions.

This Nanotechnology Undergraduate Education (NUE) in Engineering program entitled, "NUE: Improvement of Nanoscale Device Education via Theory, Experimental Design, and Characterization", at Purdue University under the direction of Dr. Michael T. Harris, will develop a new path for undergraduate students interested in developing a strong nanotechnology background that starts in their First-Year Engineering courses and can continue throughout their career at Purdue University. The components of this program span from classroom instruction through laboratory experiments and finally, to hands-on summer research programs for interested students. In particular, the educational thrusts will focus on the fabrication of novel devices for clean energy generation and storage applications, advanced bioengineered devices, and the development of sensing platforms for enhanced homeland security.

Due to the inherently interdisciplinary nature of nanoscience and nanoengineering education, the proposed projects will allow for unique extensions in the fields of chemistry, materials engineering, chemical engineering, mechanical engineering, electrical engineering, and bioengineering. Specifically, 100% of first year engineering students will be impacted (~2000 undergraduate students/year), ~200 sophomore and junior engineering students per year (~10% of all undergraduate engineering students/year), ~1% of all undergraduate students (20 engineering students/year) will participate in 3-month faculty-led research experiences through this program. Successful education of these talented undergraduate students will lead to a well-trained nanotechnology-based workforce capable of manufacturing devices for the next generation of biomedical and energy-generating devices.

Project Summary Sudden unexpected death in epilepsy (SUDEP) is a fatal complication of epilepsy that kills approximately 4,000 Americans every year. SUDEP is difficult to study because, while common, it usually occurs unobserved. The limited clinical data that exists suggests that SUDEP is a cardiorespiratory collapse that occurs directly after a seizure. Cardiorespiratory function is largely modulated by the autonomic nervous system (ANS). Sympathetic and parasympathetic autonomic nervous system pathways typically operate in opposition, so co- activation is rare. In the Oxygen Conserving family of Reflexes (OCRs), both pathways co-activate to induce breath-holding (apnea), lowered heart rate (bradycardia), and narrowing of peripheral blood vessels (vasoconstriction). Apnea prevents aspiration. Bradycardia conserves oxygen. Vasoconstriction prioritizes blood-carrying oxygen to essential organs (i.e. heart and brain). Seizure-induced autonomic disfunction, coupled with an externally triggered OCR may lead to death in Sudden Unexpected Death in Epilepsy (SUDEP). To elucidate the causal relationship between physiological parameters, OCRs, and sudden death, we propose to measure a physiological baseline of various oxygen conserving reflexes in healthy, anesthetized animals in Aim 1. This will establish a baseline for the temporal relationship between: cardiac, respiratory, and neural physiological signals in healthy animals before, during, and after OCR. It will also provide an important data set for subsequent exploration of causal relationships between those signals in both healthy and autonomically compromised subjects. Implications extend beyond SUDEP. In Aim 2 will then identify changes from the physiological baseline in various oxygen conserving reflexes for seizing animals. This will provide data of the specific role of various models of epilepsy, on compromising the autonomic system in the context of triggered OCR, and will show the unique sequence of events leading to sudden death in seizing animals. In Aim 3 we shift from acute to chronic animal models. We will determine the importance of awake, freely- behaving, chronic epilepsy on the physiological chain-of-events implicated in sudden death. We will do this using previously developed by us implantable devices to monitor the complete range of physiological parameters in chronic, freely-behaving male and female rats. Separating seizing and non-seizing, OCR vs no- OCR, responses in the same freely-moving animal over time will provide an entirely new window into the role of sympathetic and parasympathetic co-activation in normal and autonomic-compromised subjects.