2001 — 2004 |
O'grady, Scott (co-PI) [⬀] Feddersen, Rod Kofuji, Paulo (co-PI) [⬀] Boland, Linda |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Acquisition of Instrumentation For Ion Channel Research and Research Training @ University of Minnesota-Twin Cities
ABSTRACT A grant has been awarded to Dr. Feddersen at the University of Minnesota-Twin Cities to acquire scientific instrumentation that will enhance training and research opportunities concerning the influence of ions (potassium, sodium, calcium, chloride, etc.) on cell function. Changes in ionic gradients mediate diverse processes including cellular communication, chemical transportation, information storage/retrieval and energy production/use. Regulation of ion concentration is the job of selective channels traversing the membranes of all cells. While ion channel diversity and conservation among species have been revealed through the recent findings of genome projects, much remains to be learned about the basic function of ion channel proteins. Seminal advances in ion channel research have been the focus of both the Nobel prize and Lasker Award in the past year serving to draw the attention of young investigators. The goal of this proposal is to improve integration of research and research training in the field of ion channel biology which is well-represented at the University of Minnesota. Cutting-edge instrumentation will be utilized in multiple laboratory courses and time-shared with research laboratories where it will enhance 'on-the-job' research training. The award will facilitate three objectives: 1) improving the teaching capabilities of several laboratory courses, 2) expanding ion channel research opportunities for undergraduate and graduate students, and 3) providing critical infrastructure for the research training of non-university students. To meet these objectives seven state-of- the-art experimental workstations will be assembled and distributed to four courses and at least six different research labs during the year. A common method to study ion gradients and the channels that affect them requires the use of sensitive physiological approaches whereby miniature sensors(electrodes) are delicately placed in a living specimen. Individual ion channels are most conveniently studied in a simple system utilizing frog eggs. This approach involves genetic engineering and synthesis of information molecules (mRNAs) coding for ion channels followed by injection of the mRNA into large, viable egg cells. The cell's translation machinery converts the mRNA into ion channel proteins that are inserted into the cell membrane. Electrodes placed in the cell collect minute signals that report ion channel function. Using this approach researchers will measure, and instructors will teach students how to measure, the response of channels to various stimuli or blockers in the presence or absence of accessory molecules. The power of genetic engineering allows the introduction of precise mutations to pinpoint the functional importance of each part of a channel. Protein expression and functional analysis in frog eggs has become a standard approach of ion channel and cell surface receptor researchers. The instrumentation allowed by this award is well matched to that application. The equipment includes microscopes, micro-manipulators, mRNA injectors, computers, analog/digital converters, amplifiers and signal conditioning software that make ion channel recording efficient and informative. The equipment will also be used in basic electrophysiology training and research in more complex specimens such as cells in a variety of tissues, including neurons in brain slices isolated from the mature nervous system. Teaching laboratories expose students to the critical observations and techniques that provide the foundation of advanced life sciences research. The instrumentation awarded will directly support objective #1 because it will be used to present ion channel training exercises in several undergraduate and graduate level laboratory courses. Fundamentals taught in laboratory courses require an appropriate setting to advance research to the frontier of discovery. Therefore, when not needed for course work, the equipment will become a 'core utility' supplied to Principal Investigator labs for undergraduate and graduate student research projects. The contemporary, fully compatible equipment will best serve the diversity of research efforts ongoing at the University of Minnesota and satisfy objective #2. As University courses become more available and convenient for a greater diversity of students the equipment will be accessed by non-university researchers and small college educators meeting objective #3. The research instrumentation will become a distributed and unifying feature across courses and contemporary research endeavors, as well as, among individual labs within departments and research sectors. Because overall research training and research will be integrated through this award, cost-sharing funds were pledged from three separate colleges at the University of Minnesota. The funded proposal will enhance the presentation of laboratory-based education, promote student participation in the achievement of independent research goals and enrich the interaction among non-traditional students and university personnel.
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0.907 |
2011 — 2015 |
Boland, Linda M |
R15Activity Code Description: Supports small-scale research projects at educational institutions that provide baccalaureate or advanced degrees for a significant number of the Nation’s research scientists but that have not been major recipients of NIH support. The goals of the program are to (1) support meritorious research, (2) expose students to research, and (3) strengthen the research environment of the institution. Awards provide limited Direct Costs, plus applicable F&A costs, for periods not to exceed 36 months. This activity code uses multi-year funding authority; however, OER approval is NOT needed prior to an IC using this activity code. |
Lipid Modulation of Potassium Channels
DESCRIPTION (provided by applicant): Our project focuses on how potassium ion channels are modified by the actions of lipids including polyphosphoinositides and polyunsaturated fatty acids. These two classes of lipids are structural components of the cellular membrane and also act as lipid signals following certain forms of cellular communication. The fatty acids are present in oily fish, and their consumption is promoted as part of a healthy heart diet. This research has important health implications for how lipid signals impact the proper rhythmicity of heart muscle, neuronal firing patterns, memory disorders, pain and anesthesia, epilepsy, and ischemic damage during stroke and heart attack. To better understand the molecular basis for how these lipids regulate the electrical activity of cells, we will study two channels known as Kir and K2P. We use channels cloned from sponges, a valuable animal model organism, because they give us a way to understand human ion channels by comparative analysis. We will determine how the Kir channel from sponge is regulated by different polyphosphoinositides and compare this to the effects of these lipids on vertebrate ion channels. We found that the Kir channels can be modified by activating enzymes that add phosphate groups to proteins; we will determine how this phosphorylation event may interact with the regulation of the channel by lipid signals. We made a computer model of the sponge Kir channel, at the atomic level, based on atomic structural data for vertebrate Kir channels. We use this model to help predict how the lipids interact with the channel, how phosphorylation may interact with the lipids, and what specific parts of the channel may be important in determining the type of lipid that can interact with the channel. We also plan to measure the lipids in sponge cells and to investigate information in the sponge genome to predict which of the different types of these lipids may exist in the native environment of the channels. For a second type of channel known as K2P, we found that opening of the sponge channel requires the fatty acid, arachidonic acid. Previous work on fatty acid effects in vertebrate channels has implicated a certain region of the K2P channel. We will examine the role of this region for the sponge K2P channel activation by fatty acids using molecular approaches and electrophysiology. Overall, this project will help us better understand the structure-function relationships of lipid signals and ion channels. The principal investigator s an experienced ion channel biologist who has successfully mentored 40 undergraduate research students in almost 10 years at the University of Richmond. In addition to the research goals, this project provides undergraduates with meaningful research experiences and they contribute to biomedically important research, which is the main goal of the AREA grant program.
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0.922 |