Undergrad Has Sweet Success With Invention of Artificial Golgi
An undergraduate student at Rensselaer Polytechnic Institute has learned very quickly that a spoonful of sugar really does help the medicine go down. In fact, with his invention, the sugar may actually be the medicine. Among the most important and complex molecules in the human body, sugars control not just metabolism but also how cells communicate with one another. Graduating senior Jeffery Martin has put his basic knowledge of sugars to exceptional use by creating a lab-on-a-chip device that builds complex, highly specialized sugar molecules, mimicking one of the most important cellular structures in the human body — the Golgi Apparatus. “Almost completely independently he has been able to come closer than researchers with decades more experience to creating an artificial Golgi,” said Robert Linhardt, the Ann and John H. Broadbent Jr. ‘59 Senior Constellation Professor of Biocatalysis and Metabolic Engineering at Rensselaer and Martin’s adviser. “He saw a problem in the drug discovery process and almost instantly devised a way to solve it.” Cells build sugars in a cellular organelle known as the Golgi Apparatus. Under a microscope, the Golgi looks similar to a stack of pancakes. The strange-looking organelle finishes the process of protein synthesis by decorating the proteins with highly specialized arrangements of sugars. The final sugar-coated molecule is then sent out into the cell to aid in cell communication and to help determine the cell’s function in the body. Martin’s artificial Golgi functions in a surprisingly similar way to the natural Golgi, but he gives the ancient organelle a very high-tech makeover. His chip looks similar to a miniature checker board where sugars, enzymes, and other basic cell materials are suspended in water and can be transported and mixed by applying electric currents to the destination squares on the checker board. Through this process sugars can be built in an automated fashion where they are exposed to a variety of enzymes found in the natural Golgi. The resulting sugars can then be tested on living cells either on the chip or in the lab to determine their effects. With the chip’s ability to process many combinations of sugars and enzymes, it could help researchers quickly uncover new sugar-based drugs, according to Martin. Scientists have known for years that certain sugars can serve as extremely beneficial therapeutics for humans. One well-known example is heparin, which is among the most widely used drugs in the world. Heparin is formed naturally in the Golgi organelle in cells of the human body as well as in other animals like pigs. Heparin acts as an anticoagulant preventing blood clots, which makes it a good therapeutic for heart, stroke, and dialysis patients. The main source of heparin is currently the intestines of foreign livestock and, as recent news reports highlight, the risk of contamination from such sources is high. So researchers are working around the clock to develop a safer, man-made alternative to the drug that will prevent outside contamination. A synthetic alternative would build the sugar from scratch, helping eliminate the possibility of contamination he explained. “I am very grateful to have the privilege of working with Dr. Linhardt who has discovered the recipe to make fully synthetic heparin,” Martin said. “Because we know the recipe, I am going to use it as a model to test the device. If our artificial Golgi can build fully functional heparin, we can then use the artificial organelle to produce many different sugar variants by altering the combination of enzymes used to synthesize them. Another great thing about these devices is that they are of microscale size, so that if needed we could fill an entire room with them to increase throughput for drug discovery.” There are millions of possible sugar combinations that can be formed and scientists currently only know the function of very few of them like heparin. “Since it is known that these types of sugars play a part in many important biological processes such as cell growth, cell differentiation, blood coagulation, and viral defense mechanisms, we feel that that this artificial Golgi will help our team to develop a next generation of sugar-based drugs, known as glycotheraputics,” Martin said. “We are going to start making new combinations and we simply don’t know what we are going to find. We could find a sugar whose signal blocks the spread of cancer cells or initiates the differentiation of stem cells. We just don’t know.” Martin, a Barry M. Goldwater Scholar and native of the small town of Boylston, Mass., is graduating from Rensselaer on May 17, 2008 with a nearly perfect GPA. He plans to continue on at Rensselaer as a graduate student, working with Linhardt to test and further develop his artificial Golgi. [Gabrielle DeMarco @ Rensselaer Polytechnic Institute]

MIT Creates New Material For Fuel Cells
MIT engineers have improved the power output of one type of fuel cell by more than 50 percent through technology that could help these environmentally friendly energy storage devices find a much broader market, particularly in portable electronics. The new material key to the work is also considerably less expensive than its conventional industrial counterpart, among other advantages. “Our goal is to replace traditional fuel-cell membranes with these cost-effective, highly tunable and better-performing materials,” said Paula T. Hammond, Bayer Professor of Chemical Engineering and leader of the research team. She noted that the new material also has potential for use in other electrochemical systems such as batteries. The work was reported in a recent issue of Advanced Materials by Hammond, Avni A. Argun and J. Nathan Ashcraft. Argun is a postdoctoral associate in chemical engineering; Ashcraft is a graduate student in the same department. Like a battery, a fuel cell has three principal parts: two electrodes (a cathode and anode) separated by an electrolyte. Chemical reactions at the electrodes produce an electronic current that can be made to flow through an appliance connected to the battery or fuel cell. The principal difference between the two” Fuel cells get their energy from an external source of hydrogen fuel, while conventional batteries draw from a finite source in a contained system. The MIT team focused on direct methanol fuel cells (DMFCs), in which the methanol is directly used as the fuel and reforming of alcohol down to hydrogen is not required. Such a fuel cell is attractive because the only waste products are water and carbon dioxide (the latter produced in small quantities). Also, because methanol is a liquid, it is easier to store and transport than hydrogen gas, and is safer (it won’t explode). Methanol also has a high energy density-a little goes a long way, making it especially interesting for portable devices. The DMFCs currently on the market, however, have limitations. For example, the material currently used for the electrolyte sandwiched between the electrodes is expensive. Even more important: that material, known as Nafion, is permeable to methanol, allowing some of the fuel to seep across the center of the fuel cell. Among other disadvantages, this wastes fuel-and lowers the efficiency of the cell-because the fuel isn’t available for the reactions that generate electricity. Using a relatively new technique known as layer-by-layer assembly, the MIT researchers created an alternative to Nafion. “We were able to tune the structure of [our] film a few nanometers at a time,” Hammond said, getting around some of the problems associated with other approaches. The result is a thin film that is two orders of magnitude less permeable to methanol but compares favorably to Nafion in proton conductivity. To test their creation, the engineers coated a Nafion membrane with the new film and incorporated the whole into a direct methanol fuel cell. The result was an increase in power output of more than 50 percent. The team is now exploring whether the new film could be used by itself, completely replacing Nafion. To that end, they have been generating thin films that stand alone, with a consistency much like plastic wrap. This work was supported by the DuPont-MIT Alliance through 2007. It is currently supported by the National Science Foundation. In addition, Hammond and colleagues have begun exploring the new material’s potential use in photovoltaics. That work is funded by the MIT Energy Initiative. This Institute-wide initiative includes research, education, campus energy management and outreach activities, an interdisciplinary approach that covers all areas of energy supply and demand, security and environmental impact. For more information, please visit http://web.mit.edu/mitei/. [Elizabeth Thomson @ Massachusetts Institute of Technology]