Non-Invasive Mapping Ca2+ ion Concentration in subcellular Pool of organelles by Synthetic Ca2+ Sensor

This is a summer student position supervised by Javid Ahmad in Charlie McTernan's Lab.

Introduction to the Science

We are a synthetic chemistry group working in supramolecular and biological chemistry, and nanotechnology. We work with rotaxanes, catenanes and capsules to synthesise functional architectures, creating de novo catalytic enzyme analogues, artificial cellular receptors, and generating vehicles for targeted drug delivery.

About the Project

Ca²⁺ is a vital secondary messenger group and Ca²⁺ signalling forms part of the backbone of cell biology by regulating important events like post-translational modifications of proteins, protein transport to specific loci in cells etc. In cells, the endoplasmic reticulum is primary store of Ca²⁺; however, recent studies have shown that Ca²⁺ ions are also present in abundance in Golgi, making them alternate stores of Ca²⁺, though, the exact amount of Ca²⁺ there is still debatable. Likewise, Ca²⁺ stores of other organelles have also found been found to regulate their functions.

The availability of tools to map cellular Ca²⁺ in separate organelles is confined to protein-based sensors which are difficult to synthesise and use. This project aims to design a ratiometric fluorescent Ca²⁺ sensor which will be used to map Ca²⁺ concentrations in specific organelles by fluorescent non-invasive imaging. Subsequently, these systems will be used to figure out what kind of transport systems regulate Ca²⁺ concentration in different organelles. These chemically robust sensors will also be used to monitor how Ca²⁺ levels vary in diseased cells compared to normal cells. The selected candidate will learn many techniques like solid phase peptide synthesis, UV-Vis and fluorescence spectroscopy as well as cell biology assays.

About You

We are looking for a student willing to tackle exciting and challenging projects. The ideal candidate would have some knowledge of cell biology and/or organic chemistry. Any understanding of fluorescence spectroscopy will be beneficial.

References

1.         Zajac, M., Modi, S. and Krishnan, Y. (2022)

            The evolution of organellar calcium mapping technologies.

            Cell Calcium 108: 102658. PubMed abstract

2.         Suzuki, J., Kanemaru, K. and Iino, M. (2016)

            Genetically encoded fluorescent indicators for organellar calcium imaging.

            Biophysical Journal 111: 1119-1131. PubMed abstract