Dr. Kenneth Kosik wants a new way to take out the trash.
One day, his research might find a way, and if it does, 4.5 million people with Alzheimer’s disease in the United States will benefit.
The Alzheimer’s-afflicted brain looks messy. Neurons and synapses die, which results in the atrophy of key regions. The practical result is the forgetfulness that an Alzheimer’s patient experiences – with the degeneration eventually leading to the loss of language skills and the ability to care for oneself.
One protein, named for the Greek letter tau, provides the basis of Kosik’s research at UCSB. A normal cell contains tau, however according to Kosik, the protein is distributed evenly throughout. His research is focused on why the mechanisms that regulate the protein in a healthy cell fail to do so in the counterpart cells of a brain afflicted with Alzheimer’s. He said cells normally destroy any abnormalities, but that is not the case with Alzheimer’s.
“After the protein tau assembles into these long filaments, it strangles and kills the cell,” Kosik said. “If tau is becoming abnormal, why doesn’t the cell just get rid of it? Cells are very good at that. They have good mechanisms for taking out their trash.”
Kosik, who co-directs the university’s Neuroscience Research Institute and is a, molecular, cellular, and developmental biology professor, plans to investigate this unique question on campus with the help of powerful microscopy and gene sequencing techniques – and a recent $2 million grant from the Larry L. Hillblom Foundation for innovative research in Alzheimer’s disease.
For years, scientists have known of neurofibrillary tangles, the name for a type of insoluble protein aggregation in a diseased brain. Indeed, it was Kosik’s former Harvard research group that discovered tau was involved in the formation of tangles. This research, and information on another hallmark protein structure called an amyloid plaque was seen as the key to the treatment of Alzheimer’s.
As part of the work, researchers analyze volumes of raw data. In recognition of this necessary number crunching, Kosik said his team has taken an interdisciplinary approach.
“I assembled a group that brings some very unique perspectives to the problem, people with skills biologists don’t necessarily bring into their orbits,” Kosik said. “You want to have people who have strong backgrounds in computer engineering and mathematics.”
One protein in particular has the team excited. Kosik said it works to accelerate the elimination of tau in cells with abnormally high amounts, however it cannot eliminate tau fully. To learn more, Kosik said one step is to simply take advantage of the human genome, which was decoded in 2003. He also said researchers can order the protein’s gene sequence from a commercial lab – in the past, they would have had to sequence the entire string from scratch.
“It’s like a supply shop for when you take you car in,” Kosik said. “You just call up and say ‘I need a new carburetor.’ This protein that we discovered that assists in eliminating tau, not completely, but it focuses on the bad tau.”
The team also uses cells in culture in its work. Kosik said that these cultures, living in Petri dishes, are capable of displaying the same pathologies as cells in the brain. Fluorescent markers are then used to observe them under a special wavelength of light.
“Microscopy allows us to label certain proteins with a fluorescent marker,” Kosik said. “We can actually put living cells on the microscope. We [then] track the protein. It’s a very powerful technique.”
With his team of trained specialists, Kosik will spend the next four years of his grant leading the Larry L. Hillblom Center for Neurodegeneration Research at UCSB. Due to his research, perhaps taking out the trash and eliminating bad tau will soon become less of a chore.