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
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
“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.”