CBD First-Year Undergraduate Publishes Research into Eukaryotic Cellular Calcium Storage

A first-year undergraduate student in the School of Computer Science is the first author of a recently published paper describing the evolution of several proteins involved in intracellular calcium storage in eukaryotes.

The study, by Daniel Schaffer, a first-year Computational Biology major, and Drs. Lakshminarayan M.Iyer, A. Maxwell Burroughs, and L. Aravind of the National Center for Biological Information, is the first to systematically analyze a large number of proteins involved in intracellular calcium storage across the entire eukaryotic lineage.

As they reported earlier this month in the journal Frontiers in Genetics, these proteins have diverse origins and evolutionary “paths,” even though in humans they all work together on a task critical to cell survival.

“It sheds some light on the many influences on the emergence of eukaryotes and the adaptations that a lot of eukaryotes have gone through,” Schaffer said.

High calcium concentrations within cells are toxic. To control calcium concentrations, eukaryotic cells store calcium in the endoplasmic reticulum, a membrane-enclosed compartment. Proteins that control and regulate this storage are found in all eukaryotes, but Schaffer et al. report that the number and type of these proteins varies dramatically between eukaryotic groups.

“In fact,” Schaffer noted, “some proteins that are absolutely critical in humans are not found in many other eukaryotes, suggesting that they have found some novel solutions for calcium storage.”

In addition to providing insights into eukaryotic evolution, understanding this system is of importance to human health because several serious diseases occur as the result of calcium imbalances. Schaffer et al. zeroed in on one particular protein, wolframin, that is mutated in a fatal genetic disease called Wolfram Syndrome.

Schaffer et al. also studied the amino acid sequence of wolframin for clues as to its specific role in calcium storage. They report four previous unidentified functional regions, called domains, in wolframin, which they use to form a hypothesis for its role and of how it is implicated in Wolfram Syndrome.

“We hope that these domain annotations will further efforts into finding effective treatments for Wolfram Syndrome,” Schaffer said.

Schaffer is currently an undergraduate research student in the lab of the Computational Biology Department’s Professor Andreas Pfenning. He is now working on associating specific enhancers, which are regions of DNA that affect protein expression, with specific traits in mammals, under the supervision of Dr. Irene Kaplow.

This research was supported by the Intramural Research Program of the National Institutes of Health, National Library of Medicine. An earlier version of the project was presented by Schaffer at the 2019 Regeneron Science Talent Search under the title “Evolutionary Origins for Animal ER Calcium Signaling and a Proposed Role for the Channelopathy Protein Wolframin.”