The lab of Dr. Donald Gill studies calcium, one of the most fundamental signaling agents in all animal cells. Cells have evolved to precisely control Ca2+ in the cytoplasm at levels that are 10,000-fold lower than outside cells. This is accomplished by Ca2+ pumps in the plasma membrane (PM) and endoplasmic reticulum (ER).

The Gill lab studies the signals of Ca2+ that occur as a result of control of specific channels in the PM and ER membrane, which allow Ca2+ to flow into the cytosol. A slight elevation in the resting cytosolic Ca2+ level is enough to trigger rapid cellular responses such as contraction, secretion or changes in the function of key metabolic enzymes. More sustained Ca2+ signals mediate crucial longer-term responses, including cell growth, cell division, and cell death (apoptosis).

The Gill lab studies signal transduction, meaning how cells transduce external signals into Ca2+ signals. Cells sense many different external signals through specific receptors for chemical agents such as growth factors, neurotransmitters and hormones, as well as receptors for temperature, pressure, stretch, sound and light. The cell converts the message received by receptors into Ca2+ signals by precisely controlling the opening of Ca2+ channels.

The lab uses a combination of molecular biology, biochemistry, cell biology and single-cell physiological approaches to understand how the Ca2+ channels are controlled. The Gill lab uses molecular biology to mutate the channel proteins, create expression vectors and modify channel expression using gene silencing approaches.

The research also follows real-time Ca2+ signals in cells using sophisticated single cell ratiometric fluorescence imaging technology and measures the precise biophysical properties of channels using state-of-the-art electrophysiological methods. The work centers on the analysis of several distinct types of membrane channels, including members of the now widely recognized TRP family of channel proteins involved in transducing a remarkable array of external signals.

More recently, the Gill lab has focused on understanding the mechanisms by which STIM and Orai proteins are involved in controlling Ca2+ signals. This work draws together molecular and cellular approaches to understand the basic function and physiological role of these channels, which are critical to mediating essential cellular responses.