UCSB Assistant Chemistry and Biochemistry Professor Joan-Emma Shea pieces together protein puzzles using her recent Packard Fellowship for Science and Engineering.

This prestigious award, which includes a grant of $625,000 that the recipient may spend on any research costs, is, according to its website, intended to aid young, creative researchers early in their careers.

Shea is using her fellowship, which she received in October, to provide additional funds for her research group to discover how protein molecules interact and change shape. The results of this research may provide insight into illnesses such as Alzheimer’s disease and mad cow disease.

“A protein is a very large biological molecule, and it is very important in every organism,” Shea said. “The proteins function as storage entities; they function as transporters. They are important in the signaling of cells.”

Proteins come in a variety of forms, and there is no single type of protein that could accomplish all of an organism’s requirements. The fact that there are so many different types of proteins makes studying them a very wide field.

“When proteins are generated, when they are synthesized, they come out as a long chain of amino acids. Amino acids are the building block of proteins. In order for the protein to function, it has to adopt a 3-D shape. This is essentially an unsolved mystery: How do you get from a linear chain to a 3-D structure?” Shea said.

The way proteins are formed is comparable to building a metal chain. As each link is formed, the chain gets a little longer, and eventually it hits the ground. The chain will start coiling over itself and will make a pile of links. The important difference between metal chains and proteins is that the proteins must fold in a very exact and precise way rather than haphazardly falling on itself. Studying this protein folding is exactly what Shea does.

Research on protein folding has practical as well as theoretical applications. Shea said Alzheimer’s disease might be better understood through protein folding.

“If a protein does not fold correctly, very bad things can happen,” Shea said. “Proteins that fold incorrectly can associate with other incorrectly folded proteins and the associates or aggregates can grow and grow and eventually form fibrils … If you look at the brain of a patient with mad cow disease or Alzheimer’s, they will have these entities which are linked to proteins folded incorrectly. These people show signs of neurodegeneration – memory loss and tremors.”

Shea does not have a single test tube or Bunsen burner in her lab, only an array of powerful computers. Miriam Friedel, a physics graduate student in Shea’s research group, said computers provide the ability to investigate tiny molecular movements.

“Physicists have this extensive network of mathematical tools and theories,” Friedel said. “Why not apply them to biological systems to solve problems? In physics, you start with systems that are very complicated, like a protein, and model it in a simple way.”

There are two models generally used to simulate proteins. The simpler method is called a minimalist model. It excludes the effects of certain atomic interactions so that it may be processed more quickly on the computer. In contrast, the fully atomic model takes into account every interaction between atoms and demands extreme amounts of computer processing time.

“If you have a fully atomic model taking into account water and everything, you can never fold it [on the computer],” Friedel said.

Instead, the fully atomic model is useful in modeling simple protein movements or parts of proteins, Friedel explained. The two methods are complementary approaches to studying protein folding.

“Minimalist models can sometimes be useful because you can look at a longer timescale,” Friedel said.

Friedel explained how researchers once believed that the clusters of improperly folded proteins should be broken into pieces. The idea was that the protein clusters were harmful when grouped in large numbers. Data gathered from the computers has actually shown that breaking up a cluster of incorrectly folded proteins may be harmful. This is because each fragment from the original cluster may in turn grow into another cluster. The popular theory now concentrates on preventing the proteins from folding incorrectly in the first place.

“An important area of protein folding is understanding what happens during the folding process to cause them to improperly fold. If you can understand that, you can start working towards a treatment,” Friedel said.

The Packard Fellowship differs from other grants in that it allows researchers more freedom in their work. Some of the restrictions that are common in other grants include limitations on how the awarded money can be spent. In many grants awarded by the National Institute of Health, the research must be fully outlined before any money will be given. Some researchers must provide progress updates, and the money is provided incrementally after each update.

The Packard Fellowship is not subject to these restrictions. It aids more experimental research that may not produce results as quickly as conventional grants, Shea said. She said the money will be used to purchase computers and pay researchers to study protein folding.

“I was extremely lucky to get [the fellowship]. I think it recognizes UCSB, maybe more than me,” Shea said. “It will make a big difference to my research because it is a large sum of money that I can spend any way I wish. That’s something that most grants do not allow me to do.”