Raghu Padinjat
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Regulation of calcium signalling by phospholipids in vivo

Numerous human and animal diseases are thought to arise from defective “signal transduction”, the internal chemical language that cells use to monitor their surroundings and communicate with other cells. Calcium ions are an important and widespread component of this chemical language used by eukaryotic cells. Our research aims to explore how cells regulate intracellular calcium levels and understand the architecture of intracellular signalling systems.

The goal of research in the Padinjat lab is to understand how intracellular signalling cascades are engineered to deliver desired physiological functions. We focus on two evolutionarily conserved signalling cascades; those that use calcium and phosphoinositides as second messengers. We would like to understand the function of proteins that are used by the cell to generate and interpret calcium and phosphoinositide based signals. Most of our work is done using the fruitfly Drosophila melanogaster as a model system. Our work complements those of other groups in the Inositide lab and the Laboratory of Molecular Signalling who are analysing similar questions using vertebrate models.

Unlike other second messengers like cAMP, cGMP and NO, calcium is an element. Hence strategies to regulate its intracellular levels involve the activity of ion channels that allow it to enter a cellular compartment and calcium pumps that remove it from there. There are a number of different classes of ion channels that regulate intracellular calcium levels. One of these (receptor operated channels) are those regulated downstream of signal transduction pathways activated by cell surface receptors.

The transient receptor potential (TRP) super family consists of a diverse set of proteins whose primary function is to regulate the plasma membrane permeability of animal cells to a variety of ions. They are amongst the largest family of ion channels known, with representative members in many species right through from yeast to humans, and have been implicated in calcium signalling in the context of a number of different physiological pathways including transduction of light, taste, smell, mechanical and pain stimuli. Inappropriate regulation of TRP channels has been implicated in the pathogenesis of hypertension, tumour metastasis, kidney disease and sexual discrimination in males.

The primary goal of our research is to understand the identity of the second messengers that regulate TRP channel function. Although most TRP channels appear to be activated or regulated in the context of phosphoinositide hydrolysis, the identity of the second messenger that regulates channel function in vivo remains unknown and is an outstanding question in cellular calcium signalling.

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