Partners in Research
Faculty in the College of Natural Science collaborate across traditional boundaries in a wide array of research initiatives ranging from nanotechnology to the origins of the Universe and from gene expression to the bioeconomy. With more than 400 faculty affiliated with the College, research in biological, physical and mathematical sciences is synergetic with the university's goal of advancing fundamental knowledge in cutting-edge areas.
Math is at the heart of fuel cell research
Powering a car with hydrogen is more than just a job for engineers. For fuel cells to become a reality, researchers at MSU from the mathematics department to the chemistry department are working together to improve hydrogen fuel cells with polymer electrolyte membrane (PEM) fuel cell technology.
“It’s becoming increasingly clear that we must move away from extracting our fuel from the ground and into an a mode of harvesting our energy directly from ambient sources that then convert into high density fuels,” said Keith Promislow, professor of mathematics. “The models I work on attempt to make PEM fuel cells a viable component of our energy infrastructure, particularly in automotive applications.”
Promislow received funding from the National Science Foundation to focus on phase separation and ion transport. He is modeling the formation of pores and the conduction of ions within functionalized polymer electrolyte membranes. Understanding how to make membranes more cost efficient and ionically conductive at high temperatures will greatly advance the arrival of fuel cell cars to market.
Promislow works with a team that studies chemistry, physics, structure and nano-morphology of fuel cells. His role is to create mathematical models predicting how the nano-structures will function, thereby reducing the many potential combinations at the nano-scale, as it is time consuming and expensive to test all the possible outcomes. Promislow creates an overview with an ability to predict outcomes.
“Think of it like Google maps for nano-structures,” Promislow said. “You need the big picture to figure out your basic route before you can zoom in and see grandma’s house.”
Modeling can predict what sort of structures will be produced when certain chemicals are mixed together. It is a very interactive process between the chemists, mathematicians and the physicists. Promislow relays his findings to collaborators in other departments who then modify their methods accordingly.
“Finding and designing the proper energy conversion devices with the right nano-morphology is going to be central for the quality of life that we enjoy, particular at the end of the 21st century,” Promislow said. “If we do this right, the future looks very positive.”
Understanding mitochondrial regulation of health and disease
A team of scientists in biochemistry, physiology and zoology have established a research center to link mitochondrial function to global cellular processes and pathological changes that lead to aging and disease. The Center for Mitochondrial Science and Medicine aligns investigators with the National Institutes of Health initiative on Mitochondrial Medicine in Human Health.
The scientists at the center seek to identify the key cellular players in the mitochondrial life cycle and to leverage this in the design and development of therapeutics for treating diseases that have a mitochondrial component, such as Parkinson’s disease and cancer. Mitochondria are the prime energy-generating organelles in human cells. The research is directed toward understanding how energy balance through mitochondria is linked to disease progression.
“When the cell loses ability to make energy, it can affect almost all the processes in a cell,” said Laurie Kaguni, University Distinguished Professor of biochemistry and the center’s director. “Scientists have traced the root cause of many diseases to defects in mitochondrial function.”
The investigators hypothesize that improper mitochondrial function is a common theme in the development of diseases. They believe a focus on basic, system-wide, mitochondrial research will lead to new insights in treating these diseases.
A clear understanding of mitochondrial function and regulation has great potential to impact treatment of human diseases. Certain mitochondrial defects that reduce cellular energy production can cause cardiac and skeletal muscle abnormalities given that the heart and skeletal muscles have high-energy demands. Neurodegenerative diseases are also associated with reduced mitochondrial function, and in diabetes, cellular energy balance is altered. Cancer cells acquire the ability to alter mitochondrial function to satisfy their energy needs and to promote tumor survival.
Recognizing the importance of mitochondrial function, the investigators formed an interdisciplinary team to address key issues in mitochondrial research. Kaguni’s research focuses on understanding how cells reproduce mitochondria, a process called biogenesis. She examines the enzymes that replicate and transcribe mitochondrial DNA, and how failure in these processes inhibits both organellar function and reproduction.
“This organelle is actually a version of an ancient bacterium, so many of the enzymes are similar to bacterial or viral proteins,” Kaguni said. “Drugs developed against bacteria and viruses often kill mitochondria as well.”
Four other faculty members comprise the team of investigators.
- Kathleen Gallo, physiology professor, is examining how cellular signals are transmitted to and from the mitochondria, and how deregulation of these processes contributes to cancer and neurodegenerative diseases.
- Shelagh Ferguson-Miller, University Distinguished Professor of biochemistry, studies the basic biochemistry of converting food to energy, a process that occurs primarily inside the mitochondria, and is essential for life. Her laboratory has obtained some of the highest resolution crystal structures of the proteins involved, allowing scientists to visualize the process of energy production.
- John LaPres, biochemistry professor, studies how low oxygen and environmentally relevant metals influence mitochondrial function and how these processes lead to damage and diseases, such as cancer.
- Kyle Miller, zoology professor, focuses on the transport of damaged mitochondria in neurons, which may lead to new drugs for treating Parkinson’s and other neurological diseases.
A competitive Strategic Partnership Grant from the MSU Foundation funds the center’s inaugural research.
“The sum of having these investigators from different disciplines collaborate is much greater than their individual efforts, and has already led to some creative and exciting new directions,” said David DeWitt, associate dean for research. “Mitochondrial function is one of the hottest and potentially most important research areas in medical biology today, and having this collaboration of talented scientists will make advances to help diagnose, understand and treat mitochondrial diseases.”
New Protein Leads the Way in Biofuels
Fueling a vehicle made with biofuel from a rutabaga may be in the future because of research breakthroughs by a team of scientists led by biochemistry professor Christoph Benning. A newly discovered protein, Trigalactosyldiacylglycerol 4, or TGD4, is directly involved in building chloroplasts, which operate in the conversion of sunlight, carbon dioxide and water into sugars and oxygen during photosynthesis.
“Nobody knew how this mechanism worked before we described TGD4,” Benning said. “This protein directly affects photosynthesis and how plants create biomass - stems, leaves and stalks - and oils.”
The research, published in the August 2008 issue of The Plant Cell, shows how TGD4 is essential for the plant to make chloroplasts. Understanding how TGD4 works may allow scientists to create plants that would be used exclusively to produce biofuels, possibly making the process more cost-effective. Corn, soybeans and canola that are used to produce oils – accumulate the oil in their seeds.
“We’ve found that if the TGD4 protein is malfunctioning, the plant then accumulates oil in its leaves,” Benning said. “If the plant is storing oil in its leaves, there could be more oil per plant, which could make production of biofuels such as biodiesel more efficient. More research is needed so we can completely understand the mechanism of operation.”
Chloroplasts require extensive lipid movement inside the cell between the endoplasmic reticulum, where lipids are produced, and the plastid, where they are needed. In the TGD4 mutant, diacylglycerol produced in the endoplasmic reticulum is not available for galactoglycerolipid biosynthesis. This mutant accumulates diagnostic oligogalactoglycerolipids and triacylglycerol in its tissues.
Benning’s lab has started experimenting with rutabagas modified for biofuel production. They inserted a gene previously discovered by the Benning Lab that regulates the conversion of sugars into lipids called wrinkled1 into the root storage organs. In theory, this gene should cause the plant to produce much more oil throughout the plant, thereby greatly increasing the amount of harvestable oil per acre.
“To maximize efficiency, we need to make oil in not just the seeds,” Benning said. “If we could make it in the green tissues, like the leaves, stems or even underground tissues like storage roots, then we think we can make a lot more per land area.”
The research was funded by the Department of Energy, National Science Foundation and the Michigan Agricultural Experiment Station.
Benning also is a member of the Great Lakes Bioenergy Research Center, a partnership between MSU and the University of Wisconsin-Madison funded by the U.S. Department of Energy to conduct basic research aimed at solving some of the most complex problems in converting natural materials to energy.
Unlocking the Secrets of the Chloroplast
MSU scientists are unlocking the secrets of the chloroplast by taking a new approach to genetics in the Chloroplast 2010 Initiative. This new method examines the relationships between thousands of different genes and almost 100 different measurable physical characteristics, called phenotypes, in the chloroplast. The method has already led to new discoveries about gene function and relationships between previously unknown genes and important characteristics like plant oil production.
“The hope is to be able to look at the chloroplast as a system rather than a series of not necessarily obviously connected components,” said Rob Last, professor of biochemistry. “We want to go beyond the ‘one gene, one process at a time’ approach and take a more holistic approach to analyzing the data.”
Traditionally, genetics was done by choosing a phenotype that could be related to a biological process, exposing plants to a source of mutation and then sorting through the random mutants to find the phenotype of interest. Finding the gene that caused the phenotype leads to explaining how a gene controls a particular physiological process.
More recently, investigators have been reversing the process. They select two or more genes that they are interested in, and they manipulate their function. The plants are grown and the traits of interest are measured. The advantage of this process is that if the phenotype is different, then the scientists already know what gene was the cause of the change. However, the process doesn’t always work.
“A lot of the time, you do that and you don’t get an expressed phenotype for two reasons,” Last said. “The first problem is redundancy. Biological systems are extremely redundant, which is a good thing for plant survival, but to a geneticist is very problematic. If there are two genes that do more or less the same thing, sometimes, or often, the other non-altered gene will take over, preventing any change in phenotype.”
The other way Last said the approach can come up short is if the gene does something that scientists didn’t anticipate. If the gene isn’t involved in the process that is being measured, but it is involved in twenty other processes, then it will be overlooked.
“The collaborating labs at MSU are trying to take a very open ended approach toward genetics,” said Last. “We’re looking at mutants in several thousand genes instead of just one, two, ten or even thirty. We’re screening their phenotypes using 12 different screens, which all together account for about seven dozen different discreet traits that we’re measuring.”
The project creates huge amounts of data that is entered into a searchable database created at the Research Technology Support Facility. The database is searchable by gene or by phenotype, and it includes data, descriptions and photographs for different mutants. As people in the partner labs complete more analysis, the database continues to grow. As it grows, people are discovering connections between genes and functions that have never been connected before.
This broader search methodology is already showing promise toward understanding earlier MSU discoveries. In the 1980’s, Chris Somerville’s lab pioneered screening genes that were involved in making fatty acids in plant leaves. A tremendous amount of work has gone into trying to get plants to produce more oil, but so far, it hasn’t happened.
“We’ve run very similar screens to the screens that were previously run in Somerville’s lab, and elsewhere, that had been pioneered here at MSU, and we’re finding new genes they never discovered,” Last said. “New genes that influence oil production are especially valuable to MSU and Michigan because plants are being increasingly relied on to provide biodiesel fuel, fatty acid starting materials for industrial chemicals and as healthy oils for human nutrition.”
The MSU faculty involved in the project include Christoph Benning, Dean DellaPenna, Rob Last, Kenneth Nadler, John Ohlrogge, Katherine Osteryoung, Yair Shachar-Hill, Andreas Weber, Bill Wedemeyer and Curtis Wilkerson. Linda Savage is the project manager. Funding for this project is provided by the National Science Foundation.