Monday, July 9, 2012

Connecting Enzymes and Diseases - Researcher seeks insight into hepatitis C and Alzheimer’s

Connecting Enzymes and Diseases
Researcher seeks insight into hepatitis C and Alzheimer’s

July 9, 2012
By Marlene Cimons, National Science Foundation

Proteins are the body’s worker molecules, with unique shapes designed for specific tasks.
Raquel Lieberman, an assistant professor at Georgia Institute of Technology’s school of chemistry and biochemistry, is very interested in a particular protein, an enzyme that lives in the membrane of archaea, single-cell microorganisms that are similar to bacteria. Its job is to break down membrane-resident peptides, which typically are segments of larger proteins.

The enzyme from archaea is a relative of one found in humans that has several designated functions. For example, when the cells where it lives are healthy, the human enzyme generates a signaling peptide to alert the immune system that all is well. But when something is awry, the peptide either is absent, or it is present in very high amounts, a likely sign of illness.

The enzyme also plays an important but accidental role in helping the hepatitis C virus replicate, or make copies of itself, and another close relative of the enzyme produces amyloid plaques, the deposits found in the brains of Alzheimer’s patients.

“We are interested in the molecular details of how cells survive by recognizing and responding to intracellular signals,” Lieberman says, adding: “By studying the simpler model system, we might be able to better understand what might be happening in the human system. The enzyme seems to work the same way in the archaea as it does in humans.”

Ultimately, the work could provide important insights into the workings of chronic hepatitis C infection, which afflicts an estimated 180 million people worldwide, including more than 4 million in the United States, and Alzheimer’s disease, the most common form of dementia, which affects one in every eight Americans older than 65.

“If we can understand how this enzyme recognizes peptides and understand what properties of the substrate [the molecule upon which the enzyme acts] are important for that interaction, then we can start to understand the similarities and differences between this enzyme and its relatives in human diseases,” she says.

“The same enzymes are found in all these different forms of life, and do this one thing in the membrane, break down peptides,” she adds. “We want to know how they do that.”

Part of the problem in finding out these answers involves trying to work with the membranous enzyme itself, difficult because, like the cell membrane, it is hydrophobic, that is, it excludes water and is greasy. This in and of itself is a puzzle because “the chemistry of breaking down peptides requires water, so it’s the main mystery,” she says. “Where does the water come from and how does it reach the enzyme? That’s what we are trying to understand - how that chemistry really happens.”

Currently, they are trying to determine the three dimensional molecular structure of the enzyme. “When we see the shape, it will give us lots of clues as to how it works,” she says. “Determining the shape of a membrane protein is a very difficult task, however; very few scientists have succeeded in this endeavor. We are making progress, but it’s not a ‘mix-and-measure’ experiment . The process is incremental.”

Lieberman is conducting her research under a National Science Foundation Early Career Development (CAREER) award, which she received in 2009. The award supports junior faculty who exemplify the role of teacher-scholars through outstanding research, excellent education and the integration of education and research within the context of the mission of their organization. She is receiving about $850,000 over five years.

The grant also provides for education and outreach activities for younger students in the Atlanta area. Among other things, Lieberman’s lab has hosted Atlanta public high school students and their AP [Advanced Placement] biology teachers, and is developing a two-week summer science camp for local middle-school students.

“We’ve had high school students come in and learn how to determine the structure of a protein,” Lieberman says. “More recently, we’ve developed educational materials to teach students how evolution works, from archaea to humans. We created the materials and are sharing them with other high school science teachers in the area.”

They combine art with science, “which is one of the really cool aspects,” she says. “We use computer graphics and other engaging activities that are fun for kids. Students can see on a computer screen how amino acids, the building blocks of proteins, come together to give a protein the characteristic shape it needs to perform its function. The amino acids are encoded by DNA, which gets transmitted to family members.

“Students then go and question their family members about their medical history,” she adds. “Interestingly, most students have no idea what diseases are in their families. By learning their own personal medical information, they also learn about genes and genetics.”

1 comment:

  1. Enzymes are biological molecules that catalyze chemical reactions.A living system controls its activity through enzymes. An enzyme is a protein molecule that is a biological catalyst with three characteristics. First, the basic function of an enzyme is to increase the rate of a reaction. Most cellular reactions occur about a million times faster than they would in the absence of an enzyme. Second, most enzymes act specifically with only one reactant to produce products. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates sufficient for life. Since enzymes are selective for their substrates and speed up only a few reactions from among many possibilities, the set of enzymes made in a cell determines which metabolic pathways occur in that cell.