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MAES Researcher Identifies Cell Mechanism Leading to Diabetic Blindness

Susanne MohrScientists have long known that high blood sugar levels from diabetes damage blood vessels in the eye, but they didn't know why or how. Now an MAES scientist has discovered the process that causes retinal cells to die, and that discovery could lead to new treatments that halt the damage.

Diabetic retinopathy is a common side effect of diabetes and the leading cause of blindness in young adults in the United States.

Innovative research by Susanne Mohr, MAES physiology researcher, found the siah-1 protein is produced by the body when blood sugar levels are high. She then discovered that the siah-1 protein serves as a type of chauffeur for another protein, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), shuttling the GAPDH into the nucleus of Müller cells, special cells that have contact with the blood vessels in the eye. When GAPDH accumulates in their nuclei, the Müller cells die. Their death leads to the vascular damage associated with diabetic retinopathy.

The research was published in the Jan. 29 issue of the Journal of Biological Chemistry.

"Our earlier research showed that high glucose levels cause GAPDH to accumulate in the nuclei of Müller cells in the retina," Mohr explained. "But we weren't sure how the GAPDH was getting in there. It doesn't contain any of the necessary signaling motifs. I read about the siah-1 protein and cell death in white blood cells in a Nature paper, so we decided to investigate them. We had no idea if the siah-1 protein was even in the retina."

Mohr's research also found that lowering levels of siah-1 proteins stopped GAPDH from moving into the nuclei of Müller cells and stopped them from dying.

"This is very exciting," Mohr said. "We know that we can't regulate production of GAPDH because it's necessary for producing energy throughout the body. But since siah-1 is produced only when glucose levels are high, regulating it doesn't cause any problems. If we can figure out how to stop siah-1 production, it may lead to new treatments for diabetic retinopathy."

Mohr explained that stopping GAPDH from moving into Müller cell nuclei is important to halting the progress of diabetic retinopathy. Even after glucose levels are lowered and stabilized in diabetics, GAPDH continues to accumulate in Müller cell nuclei. So the retinal damage keeps worsening, just more slowly. Between 40 and 45 percent of people diagnosed with diabetes have some degree of diabetic retinopathy.

"If we can keep GAPDH out of the nuclei, we may be able to completely stop diabetic retinopathy," Mohr said. "Our next step is to figure out if both the GAPHD and the siah-1 proteins have to be together in a complex to cause cell death."

E. Chepchumba Yego, doctoral student at Case Western Reserve University, is co-author of the paper. Mohr began the research at Case Western and then continued the project when she joined MSU in August 2009.

The research is funded by the National Institutes of Health and supported by the Michigan Agricultural Experiment Station.

Biofuel Crop Diversity Adds Value, MAES Researchers Say

Diverse biofuel plantings such as native prairie attract more beneficial insects than do single crops such as corn, MAES scientists find. Biofuel policies should take such added value into account, they urge, based on their pioneering studies of beneficial insects in biofuel crops.

Lady beetles, bees and other beneficial insects provide numerous ecosystem services, including controlling pests and pollinating crops. Earlier research by MAES scientists estimated that predator insects in soybeans provide about $240 million worth of biological pest control per year in the United States.

Doug Landis"We found that the diversity of the plants has a direct effect on the number and diversity of beneficial insects," said Doug Landis, MAES entomologist and co-author of the study, which is published in a special issue of the journal BioEnergy Research. "As policymakers consider which biofuel crops to support with incentives, we want to make sure they know about all the benefits provided by a range of crops. Some of these benefits, such as greenhouse gas benefits, pest suppression and pollination, are not currently being counted."

The scientists compared beneficial insect populations in three types of biofuel crops: corn, switchgrass and mixed native prairie (native grasses and wildflowers).

The research points out that there are advantages and disadvantages to each type of crop. Corn does provide more biomass per acre, but switchgrass and prairie attract greater numbers of beneficial insects, more diverse types of beneficial insects, or both in some cases.

Rufus Isaacs"While there were similar numbers of bee species in each crop, the abundance of bees was three to four times higher in switchgrass and native prairie than in corn," said Rufus Isaacs, MAES entomologist and study co-author. "There has been concern in the United States about declining numbers of pollinators. As policies are developed to increase production of cellulosic biofuels, it's important to know how the type of biofuel crop affects the environment and biodiversity, as well as how much fuel it can produce."

Landis and Isaacs cautioned that if switchgrass is managed as a biofuel monoculture, some of the plant diversity they observed in their study fields could be lost, making the crop less suitable for beneficial insects.

Both Landis and Isaacs are members of the Great Lakes Bioenergy Research Center. That partnership between Michigan State and the University of Wisconsin-Madison is funded by the U.S. Department of Energy to conduct basic research aimed at solving complex problems in converting natural materials to energy.

"This is the first step in a series of studies aimed at characterizing biofuel landscapes of the future, landscapes that are economically and environmentally sustainable," Landis said. "This research suggests that monocultures probably won't offer the long-term benefits that more diverse landscapes will. The next step in our work will be to put a value on the services beneficial insects provide. We'll be measuring how much predation and pollination is taking place."

In addition to Landis and Isaacs, other paper authors are Mary Gardiner, former MSU entomology post-doctoral researcher who is now assistant professor of entomology at Ohio State University; Julianna Tuell, MSU entomology post-doctoral researcher; Jason Gibbs, doctoral student at York University; and John Ascher, manager of the Bee Database Project at the American Museum of Natural History.

This research was funded by the DOE Great Lakes Bioenergy Research Center, the Michigan Agricultural Experiment Station and the U.S. Department of Agricultural National Research Initiative program.

MAES Grant Writing Workshop Continues to Receive Rave Reviews

"Best continuing education session I have attended in five years!"

"Bravo! Please come back!"

"Attending this seminar, I am now able to identify problems in a grant that I never could have without such a lecture."

"It saved me a lot of time, as I am on the verge of putting together a National Institutes of Health application as a principal investigator."

Very engaging and enthusiastic speaker. Excellent use of common examples to illustrate concepts."

These were just a few of the enthusiastic evaluations of the third MAES Preawards Office-sponsored "Write Winning Grants" workshop on Jan. 6. The workshop -- attended by 134 people representing more than 60 departments across the university -- featured presenter David Morrison of Grant Writers’ Seminars and Workshops, who addressed both the practical and conceptual aspects of successful proposal writing.

"Dr. Morrison is an outstanding presenter," said John Baker, MAES associate director. "He talked about some of the nuanced things that professors need to consider when writing grants but don’t always think about, as well as grant-writing basics. Though the seminar is extremely valuable for new faculty members, senior faculty members that have participated find it very useful."

Morrison, who received a doctorate in molecular biology and biophysics from Yale and served as associate director of research at the University of Kansas Medical Cancer Center and director of medical research at St. Luke’s Hospital in Kansas City, is a member of multiple national review panels and advisory groups and has a long history of writing successful grant proposals. He discussed how to write proposals aimed at reviewers and how to identify the most appropriate granting agency. Workshop attendees had the option of purchasing workbooks devoted to the grant subtleties of specific federal agencies, such as the U.S. Department of Agriculture or the National Institutes of Health.

First-time and novice grant writers weren’t the only participants who found value in the workshop.

"I've had some success in writing grants," said Stephen Gasteyer, MAES sociology researcher, "but I found Dr. Morrison's emphasis on how to construct the opening page of an application from the title all the way through those first sets of paragraphs to be very helpful. Knowing how to put together an effective opening page can really draw in the reviewers so they can immediately see the importance of what you are trying to do."

"Although I am an experienced grant writer and teach grant writing, the program had a lot of very useful concepts and advice that reinforced some of my own ideas," said Nigel Paneth, university distinguished professor of epidemiology and pediatrics. "For example, the concept of precisely where in the innovation cycle your best position is rang very true to me, because you can be a little too innovative and you can be insufficiently innovative; hitting the innovation 'sweet spot' is key. I’ll definitely be incorporating some of these ideas into my teaching."

The next seminar is scheduled for Jan. 6, 2011. For more information, contact Candace Ebbinghaus at candy@msu.edu or 517-355-0123, ext. 112.

Renewable Energy Policies and Business and Climate Change are Topics of March Bioeconomy and Global Climate Change Lectures

Climate change's implications for business and the effects of renewable energy policies are the focus of the next two lectures in the yearlong Bioeconomy and Climate Change Distinguished Lecture Series, sponsored by the MAES. The series is intended for all people working on climate change, both at MSU and outside the university.

Richard SchmalenseeOn March 4, Richard Schmalensee, of the Massachusetts Institute of Technology, will discuss renewable energy policies. Schmalensee is the Howard W. Johnson professor of economics and management at MIT and director of the MIT Center for Energy and Environmental Policy Research. His research looks at industrial organization economics and its application to managerial and public policy issues, with particular emphasis on antitrust, regulatory and environmental policies.

His talk will run from 1 to 2 p.m. in Parlor C of the MSU Union. A reception follows.

Bjorn StigsonOn March 22, Björn Stigson, president of the World Business Council for Sustainable Development, will discuss climate change and business. Stigson provides advice to the Chinese government, the Dow Jones sustainability indexes, the Harvard University Kennedy School of Government, the Clinton Global Initiative and the Global Reporting Initiative.

His talk is scheduled for 1 to 2 p.m. in Parlor C of the MSU Union. A reception follows.

Reminder: Terry Root, senior fellow at the Woods Institute for the Environment at Stanford University, will present "Climate Change and Michigan Species: Adapting or Going Extinct" on Feb. 4 as part of the lecture series.

The lecture series is organized by Thomas Dietz, assistant vice president for environmental research, and Jinhua Zhao, MAES economics and agricultural economics researcher.

There is no charge to attend the lectures, but attendees are asked to preregister. For more information or to RSVP, visit the distinguished lecture series Web site.

Climate Change Symposium Seeks Proposals for Sessions and Posters

To build on discussions started by the Distinguished Lecture Series on the Bioeconomy and Global Climate Change, organizers of the symposium "Climate Change Vulnerabilities and Opportunities: Michigan and Beyond" have issued a call for proposals for research and informational sessions, as well as posters. The symposium, sponsored by the Michigan Agricultural Experiment Station, will take place April 26-27, 2010, at the Kellogg Center on the MSU campus.

Topics will range from the economic and social effects of climate change and business and government response to adaptation strategies and the challenges and opportunities of a green economy.

Research sessions should present results from multiple scientists that address a common theme. Informational sessions can be workshops, roundtable discussions or descriptions of programs. Both research and informational sessions should be 90 minutes long. Posters can highlight research results or describe programs.

To submit a proposal for a session or a poster, visit the symposium submissions Web site. All proposals are due by Feb. 15.

The symposium is organized by Tom Dietz, MSU assistant vice president for environmental research, and Jinhua Zhao, MAES economics researcher. For more information, visit the symposium Web site.

MSU, African Educators Expand Agricultural Education

MSU researchers, including two MAES scientists, will use a $1 million grant from the Bill & Melinda Gates Foundation to help African educators develop free and open access to agricultural education material, which they hope could improve agricultural practices and build a sustainable economy.

AgShare Open Education Resources is an 18-month pilot project. African educational institutions – still to be identified – will create a virtual hub of resources and curriculum for master of science degrees in agriculture, with areas of emphasis in livestock, crops and agribusiness.

Among beneficiaries of the project are faculty and student researchers from various agricultural universities in Africa, representatives of nongovernmental organizations and farmers from around the continent.

"The project comes at an important time for African institutions, which are looking for effective ways to address the development of their educational agriculture programming with limited financial resources," said Christine Geith, assistant provost and executive director of MSUglobal Learning Ventures, an entrepreneurial business unit.

MSU faculty members will work with OER Africa, a new project headquartered in Nairobi, Kenya, and other international experts to develop best practices for sharing information through open education resources. This is an educational learning trend in which materials reside in a public domain for users to freely share and repurpose.

AgShare will allow users to form learning networks that will share content such as modules, textbook material and videos via the Web. In remote areas where the Internet is less readily accessible, information will be distributed through DVDs and printed material.

The research team includes MAES researcher John Kaneene, university distinguished professor of epidemiology, and MAES telecommunications researcher Cliff Lampe.

John Kaneene"Africa's agriculture industry requires improved higher education, research, training and outreach programs," Kaneene said. "Without improved dissemination and building of shared resources, the producers and educators will rely on 19th-century word-of-mouth education. This project is critical to sustainable agriculture in Africa."

Currently, university-based agricultural education programs in Africa are severely hampered by out-of-date graduate teaching materials coupled with inadequate funding to purchase new materials, he added.

"Higher education plays a critical role in developing the practices and resources necessary to dramatically boost agricultural yields in the developing world," said Khalid Bomba, a senior program officer in the Agricultural Development initiative at the Bill & Melinda Gates Foundation. "AgShare Open Education Resources has the potential to provide Africa’s future scientists and leaders with access to current educational materials, enabling them to create innovative solutions for small farmers."

Nutrient Management Workshop Set for Feb. 2

Small and medium-sized dairy farm operators are invited to learn about nutrient management issues, resources and opportunities at a one-day workshop hosted by the W.K. Kellogg Biological Station (KBS) in Hickory Corners Feb. 2

Participants who attend the 9 a.m. to 5 p.m. workshop will hear from MAES scientist Wendy Powers, director of environmental stewardship for animal agriculture; Richard Leep, MAES crop and soil scientist; Dana Kirk, biosystems and agricultural engineering visiting specialist; Charles Gould, MSU Extension educator; and Mark Powell, U.S. Department of Agriculture soil scientist in the Dairy Forage and Aquaculture Research Unit.

Attendees can expect to learn about reducing air emissions from dairy facilities through ration balancing, receive the latest information on anaerobic digesters and find out about managing nitrogen fertilizer in pastures. On-farm composting and details about the Michigan Agriculture Environmental Assurance Program (MAEAP) will also be discussed.

Mat Haan, KBS pasture-based dairy project manager, said dairy farmers and managers interested in learning about nutrient management issues that apply specifically to small and medium-sized farms will find the workshop valuable.

"Nutrient management is an issue challenging farms of all sizes," he said. "But it's important to take into consideration that smaller farms may need to approach the management process a bit differently than larger facilities do. Knowing what tools and resources are available for small and midsized farm operators is a critical first step in the process."

Haan noted that there will be ample opportunity for attendees to network with fellow workshop participants and the speakers during the day.

After the workshop, attendees may take a guided tour of the KBS Pasture Dairy Research and Education Center and robotic milking facility.

Registration is $40 per person and includes lunch, snacks and materials.

To register for the nutrient management workshop or to receive additional information, contact Mat Haan at 269-671-2360, send an e-mail to haanm@msu.edu or visit the workshop Web site.

MAES Helps Fund Studies on Climate Change, Food Production in East Africa

For the first time, crop breeders and agricultural specialists in East Africa will have regionally specific climate data to research and manage crops in an effort to improve food production.

Using a $430,000 Rockefeller Foundation grant, Michigan State University researchers will study the impact of climate change on the drought-stricken area, which includes Kenya, Tanzania and Uganda, said lead researcher Jennifer Olson, associate professor in the College of Communication Arts and Sciences.

"This part of Africa is getting over the worst drought it has had in many years," said Olson, who is working with geographers, agronomists, sociologists and climatologists at MSU and in East Africa. "Climate change is leading to warmer temperatures and heightened water stress for plants, as well as less reliable rain."

With assistance from an MSU supercomputer and the Michigan Agricultural Experiment Station, the research team will link a customized regional climate model with crop and water models. This will enable agriculture specialists to determine the impact of climate change on various crop varieties. As a result, they will develop crop varieties that better withstand climate change.

"The models we create can test the effectiveness of new crop varieties in responding to warmer temperatures and other climate changes," Olson said, "and the results will speed up the agricultural research cycle."

Communicating the findings to agricultural researchers and policymakers will require innovative approaches such as interactive visuals that illustrate model results, she added.

"Most of our research has focused on the causes and consequences of climate change," said Nathan Moore, assistant professor in the Department of Geography and co-investigator on the project. "This grant will apply those results in a new way by asking African specialists what their information needs are and how they want us to help. The project also will allow us to train African researchers how to analyze crop-climate data so they can test different possibilities themselves."

MSU's long-standing commitment to African research will aid the project’s success, said Jeffrey Riedinger, dean of MSU International Studies and Programs.

"Throughout the past 50 years, MSU has established valuable connections in Africa, a great network of partners in the region and significant scholarship there," he said.

Sea Lamprey Research Featured on MSU Today

Weiming Li, MAES fisheries and wildlife scientist, identified the pheromone that male sea lampreys use to lure lady lampreys to their nests. He and his colleagues then developed a synthetic version that holds promise as a control for the invasive species. U.S. and Canadian governments spend about $10 million to $15 million each year to control the destructive parasites.

Show 15 of MSUToday, which produces MSU feature stories for the Big Ten Network, reports on research to evaluate the synthetic pheromone as a control method.

MAES Researcher Links Diabetic Complication, Nerve Damage in Bone Marrow

Julia BusikA research team led by an MAES scientist has discovered a link between diabetes and bone marrow nerve damage that may help treat one of the disease's most common and potentially blindness-causing complications.

The key to better treating retinopathy -- damage to blood vessels in the retina -- which affects up to 80 percent of diabetic patients, is not in the retina but in damage to the nerves found in bone marrow. That damage leads to abnormal release of stem cells, said Julia Busik, MAES physiology researcher.

"With retinopathy, blood vessels grow abnormally in the retina, distort vision and eventually can cause blindness," said Busik, whose research appears in a recent issue of the Journal of Experimental Medicine. "There has been a lot of progress in treating the complication, but most treatments use a laser that is painful to the patient and destroys parts of the retina."

Busik and her team found that nerve damage in diabetic bone marrow -- where stem cells known as endothelial progenitor cells (EPCs) reside -- affects the daily release of those EPCs into the bloodstream. Normally EPCs would exit the bone marrow and repair damage done in the vascular system during sleep.

Using animal models, the research team observed that the pattern of EPC release is faulty in diabetic bone marrow, creating abnormally low levels of EPCs during sleep, when they are needed most. That decrease in EPC release from a diabetic patient's bone marrow preceded the development of retinopathy.

"When the bone marrow suffers nerve damage in diabetic patients, it no longer provides a signal for the timely release of these reparative stem cells," Busik said.

The results suggest that bone marrow nerve damage represents a new therapeutic target for treatment of all diabetic vascular complications, such as retinopathy.

"This opens up new avenues to better treatments outside of the retina that focus on stem cells and the causes of the nerve damage in bone marrow," said Busik, whose collaborators included other researchers at MSU and the University of Florida. "We know what happens in the retina and have treatments that are very invasive; we now can look at a host of other options."

Those options include looking at ways to prevent the nerve damage in the bone marrow and potentially repairing or replacing the damaged endothelial progenitor cells.

This research is funded by the National Institutes of Health, the Juvenile Diabetes Research Foundation and the Michigan Agricultural Experiment Station.

Future work needs to be done to explain why the nerve damage in bone marrow occurs in diabetic patients to begin with, Busik said.

Last Updated: January 29, 2010
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