This CAREER award by the Biomaterials program in the Division of Materials Research is to Michigan Technological University. The award is cofunded by the Biomedical Engineering program in the Chemical, Bioengineering, Environmental, and Transport Systems. Current research shows that the regulation of iron ions in human body is crucial for healthy function of our brain, and in reducing the incidence of Parkinson or Alzheimer's diseases. In human body, this important task is accomplished by proteins called 'ferritins'. Ferritin proteins store iron ions when their circulating amount exceeds the required amount, and ferritins release iron ions when the body lacks sufficient iron to perform its normal functions. The ferritin proteins store iron ions in the form of crystals with well-defined atomic arrangements and chemistry. This process is called biomineralization. While these unique proteins have been the subject of intense research in biology and chemistry fields due to their importance in many chronic diseases, little effort has been made to unveil the dynamics of such biomineralization processes in liquid conditions. This proposal will address this shortcoming by studying the biomineralization process inside the proteins in real time at atomic scales. A potential outcome of these studies would be in developing novel approaches in the early detection and treatment of some these neurological diseases. By better understanding the role of iron storage in proteins, it may be easier to develop new pharmaceutical drugs to correct the ferritin dysfunctions. As part of the teaching, training and outreach activities, special attention will be given in recruiting and mentoring female and underrepresented students to work in the investigator's research laboratory. In addition, a new course will be developed to educate undergraduate and graduate students on the recent developments in this field of biomineralization. To increase public awareness, this project plans to distribute the results of this project through press coverage, news releases and social media. Radio talk shows to discuss the new horizons on reducing neuro-degenerative diseases such as Parkinson or Alzheimer's are also part of this project.

Technical Abstract

This CAREER award by the Biomaterials program in the Division of Materials Research to Michigan Technological University is in developing an understanding the role of biomineralization and demineralization processes with ferritin proteins, and to study iron transport in the human body with the goal of understanding the fundamental differences among different ferritins responsible for neurological diseases. This award is cofunded by the Biomedical Engineering program in the Chemical, Bioengineering, Environmental, and Transport Systems. Ferritin proteins convert ferrous irons to ferrihydrite and iron oxide crystals through a complex biomineralization process in the body. Ferritins play an important role in iron transport, and thus protecting the body from iron ion toxicity. Any dysfunction in ferritin protein may result in chronic diseases due to iron toxicity including neurological ones. Therefore, understanding the process of biomineralization by ferritin is of great importance in the study of neuro-degeneration and other chronic diseases such as Parkinson or Alzheimer's. The proposed research probes are expected to understand the biomineralization processes within different ferritins with respect to nucleation, growth mechanism, existence of defects, and morphology of healthy and dysfunction ferritin. Using liquid electron microscopy with subnanometer scale resolution, this award will study the biomineralization and/or demineralization processes inside a ferritin protein in solution, and in real time. The broader impacts of this CAREER award would be in integrating undergraduate and graduate education in teaching and training with this multi-disciplinary research at all levels while promoting diversity. Graduate and undergraduate students involved with the project will be trained in emerging fields such as in-situ electron microscopy and biomineralization. A new graduate course will be developed for senior undergraduate and graduate students. The investigator and graduate students will work with minorities and underrepresented students in the proposed research activities. As part of this project, this researcher will recruit female/minority students for undergraduate education through well-established outreach programs at Michigan Technological University

Agency
National Science Foundation (NSF)
Institute
Division of Materials Research (DMR)
Application #
1350734
Program Officer
Joseph A. Akkara
Project Start
Project End
Budget Start
2014-07-01
Budget End
2015-10-31
Support Year
Fiscal Year
2013
Total Cost
$160,000
Indirect Cost
Name
Michigan Technological University
Department
Type
DUNS #
City
Houghton
State
MI
Country
United States
Zip Code
49931