Participant: PROMISE AGEP Research Symposium
Department: Biological Sciences Department
Institution: University of Maryland Baltimore County (UMBC)
Anoxia Tolerance in Zebrafish Embryos
Oxygen is essential for the production of ATP (the main energy source of the cell) in aerobic organisms. Molecular oxygen is the last electron acceptor in the electron transport chain of oxidative phosphorylation (major ATP producing metabolic pathway). Therefore pathological conditions such as ischemia (reduced blood flow) that diminish oxygen availability are a major cause of morbidity and mortality. Current treatments, rather ineffectively, aim to induce a hypometabolic state (low turnover of ATP) in order lessen the damage caused by ischemia. In nature many organisms have adaptive mechanisms that allow them to achieve a hypometabolic state in the face of energetic stress. Identification of these mechanisms is expected to provide insight on novel therapeutic treatments for ischemia-induce injury. We are investigating how hypometabolism is achieved using zebrafish as a model organism. Zebrafish embryos demonstrate a remarkable ability to suspend animation during embryogenesis in response to anoxia (zero oxygen), and ultimately resume development when normal oxygen conditions are restored. This arrested state is marked by cessation of ATP demanding processes such as proliferation and transcription. We hypothesize that anoxia causes a blockage in the electron transport chain, resulting in a change to a cellular metabolite. Thereby activating a kinase that acts on downstream targets to orchestrate arrest. Our working hypothesis is that AMP (metabolite resulting from ATP consumption) signals through AMPK (a well-characterized enzyme important for cellular homeostasis) to orchestrate arrest and conserve ATP. We will investigate the role of AMP in signaling arrest by subjecting early stage embryos to drug treatments using an AMP analog, AICAR. Then we will examine the effects on its ability to arrest under anoxia. These studies will be among the first to provide molecular insight into how vertebrates achieve a hypometabolic state.
Ikenna Okafor is in his first year of graduate study in the Biological Science department at University of Maryland, Baltimore County. He is currently investigating developmental biology in zebrafish under the mentorship of Dr. Rachel Brewster. In May 2017, he will graduate with a Master of Sciences degree in Biological science. Mr. Okafor is also a recipient of the prestigious Louis Stokes Alliance Bridge to Doctorate National Science Foundation fellowship. He remains an active member of Graduate Student Association of Biological Sciences. In May 2013, he received is Bachelor of Sciences in Neuroscience from George Mason University. Prior to graduate study, Ikenna actively participated in a breadth of research experiences ranging from social neuroscience to neural engineering.
Outside of academia Ikenna is passionate about encouraging STEM career paths to underrepresented youth, exemplified through his work as a mentor for the National Society of Black Engineers Summer Engineering Experience for Kids. After earning his PhD in molecular biology/Genetics, he plans to establish programs that encourage STEM education in countries developing countries around the world.
GENERAL SUMMARY OF GRADUATE RESEARCH
The Brewster Lab studies mechanisms of development using zebrafish as a model system. My work focuses heavily on metabolism during embryogenesis. Zebrafish display a remarkable ability to withstand energetic stress by inducing a hypometabolic for a 24 hour time period. We hypothesize that there is a proximal signal that senses the harsh environment and subsequently acts on downstream targets to orchestrate arrest. We are utilizing a variety of molecular biological techniques in order to elucidate the key signaling molecules of this pathway including genetic manipulation, immunolabeling and mass spectrometry. Our goal is to establish zebrafish as a vertebrate model for a studying anoxia tolerance.
PRESENTATIONS AND PUBLICATIONS
- Poster, April 2013: “CA3 Removal of Hippocampus”- Sixth Annual VA/NC Alliance for Minority Participation Research Symposium, Virginia Commonwealth University.