He says, “When proteins are made by our cells, they consist of a long string of amino acids that all have to fold into a specific 3-D shape in order to function properly. That folding happens with the aid of little chaperone proteins, little helpers, who help get that protein in the exact shape it needs to be to do its job. When the protein tau is healthy, it helps hold the cell in its proper shape, like scaffolding supports a building. When the protein misfolds it doesn’t get into the correct 3-D shape, which can cause the protein to stick together with other misfolded proteins, forming clumps. These clumps of misfolded proteins are called aggregates and it’s a common feature in neurodegenerative diseases.”
“So,” Anderson says, “in my particular project, I run experiments using baker’s yeast. I give the yeast the ability to produce the protein tau – meaning the normal, folded, healthy version of tau. And then I try to find what conditions I can manipulate to cause tau to misfold and aggregate/clump together. If those conditions are found, it would be the model for neurodegeneration.”
“If we can discover those conditions in yeast,” Schiavo underscores, “it’s possible that similar conditions may be at play in the neurons in our brains.”
He explains that yeast is a valuable asset to biochemists because the cells in yeast and the cells in humans have the same method of protein production and protein folding. Yeast is also cheaper and easier to come by than brain neurons if you need to run an experiment.
Approaching tau misfolding and aggregates from a slightly different angle, Schiavo’s project attempts to establish a molecular link (what we eat) to protein folding.
Schiavo came up with the idea to put the yeast on a low-carb diet and then to observe the effect on protein folding. He brought the idea to Holmes who found a way to integrate his research within the framework of the lab’s existing projects. Holmes fine-tuned Schiavo’s proposal, submitted it to the Rhode Island Foundation and was granted a $10,000 medical research grant to investigate the connection between metabolism (absorbing the nutrients we eat) and protein health.
“It’s a very new field,” Schiavo explains. “Not a lot of work has been done yet on the molecular issues behind protein folding.”
The research students in this lab not only run experiments, they write scientific papers on their findings. Anderson has worked in Holmes’ lab for the past three years and has presented at RIC’s annual Center for Research and Creative Activity Poster Sessions and at the annual Rhode Island Summer Undergraduate Research Fellows (SURF) Conference at URI. She has also attended a scientific conference with Holmes on Alzheimer’s disease and a Protein Society Conference with Holmes, where she presented a poster.