Professors Publish Paper in ‘Cell’

Kim Caldwell and Guy Caldwell
Dr. Kim Caldwell and Dr. Guy Caldwell co-authored a paper that was published in a January edition of the journal Cell.

From the February 2014 Desktop News | Work done in a University of Alabama laboratory shows that genetically engineered variants of proteins may be “highly promising” for eventually halting the progression of neurological diseases such as Parkinson’s and Lou Gehrig’s disease, according to a paper co-authored by UA researchers and published in the Jan. 16 edition of the journal Cell.

Dr. Guy Caldwell and Dr. Kim Caldwell, both professors in the Department of Biological Sciences, published the paper together with Bryan Martinez, a third-year doctoral student and 2010 biological sciences graduate, and researchers at the University of Pennsylvania.

The report indicates that variants of a chaperone protein called Hsp104, which is naturally found in single-cell organisms, may be able to prevent protein clumping in multi-cellular organisms, a phenomenon often associated with multiple neurological diseases.

Chaperone proteins, like Hsp104, regulate activities associated with protein folding, or the process by which proteins assume a functional shape. When proteins do not fold properly, they malfunction, which often causes other proteins to misfold, ultimately leading to the formation of protein aggregates, or clumps. In patients with neurodegenerative diseases, protein clumping leads to neuron malfunction and death.

In the UA lab, reprogrammed protein variants, engineered in yeast by the University of Pennsylvania lab, rescued neuron loss associated with protein clumping typical of Parkinson’s patients.

“We have engineered a yeast protein to essentially improve upon its natural activity and to function better in more complex biological systems,” said Guy Caldwell, one of the University’s three co-authors of the journal article.

UA scientists collaborated with researchers from the lab of Dr. James Shorter at the University of Pennsylvania, including the paper’s lead author Dr. Meredith E. Jackrel. UA’s portion of the research was funded by the National Science Foundation and the National Institutes of Health.