MULTIFACETED CASR

"The role of the Calcium Sensing Receptor (CaSR) in health and disease, implications for translational medicine."

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 Obiettivo del progetto (Objective)

'The identification of the extracellular calcium sensing receptor (CaSR) was a crucial step in understanding nutrient sensing in mammals. In mammalian organisms the CaSR has multiple roles: besides calcium homeostasis, it is involved in protection against osteoporosis, blood vessel calcification, prevention against colorectal cancer, is involved in metastasis of breast and prostate cancer cells to bone. The proposed ITN will perform basic and multidisciplinary investigations into the role of the CaSR and will provide experimental data for computational modelling. It will use holistic approaches of systems biology to gain knowledge on mechanisms of CaSR function. We will use intersectoral expertise in revealing the significance of CaSR signalling in cancer, and cardiovascular disease. The purpose of this ITN is to: • Educate and train Early Stage Researchers to become excellent scientists, enable them to gain a holistic view of their specific research area, prepare them for the challenges of working in a highly competitive environment, be it in Academia or in Industry. • Generate a systems biology model for CaSR-dependent signalling in order to find innovative therapeutic approaches and interventions for the natural and synthetic ligands of the CaSR. • Establish long lasting interdisciplinary and intersectoral cooperation among basic, clinical and applied researchers, working on the CaSR to strengthen the European Research Area.

Being in a research environment that examines the role of one single molecule in many different tissues (e.g. kidney, intestine, blood vessels) and pathologies (cancer and vascular calcification), will increase the awareness of the young researchers for a holistic approach in understanding CaSR-related pathophysiology. Continuous comparison of the function of the CaSR in systems studied by their fellow ESRs, will sensitize the young researchers for the complexities of biomedical research and advantages of multidisciplinarity.'

Introduzione (Teaser)

Calcium is one of the most versatile and widely used signalling agents in mammalian cells. Disturbances in calcium signalling are common in many human diseases.

Descrizione progetto (Article)

The extracellular calcium sensing receptor (CaSR) is used by cells to detect changes in extracellular calcium concentration and is the main regulator of systemic calcium homeostasis. It also regulates hormone secretion, gene expression, ion channel activity, modulation of inflammation and differentiation, and therefore represents a key molecule in functional physiology.

The (CaSR) is therefore one of the most promising therapeutic targets for diseases where calcium is implicated. The EU-funded initial training network 'The role of the calcium sensing receptor (CaSR) in health and disease' (MULTIFACETED CaSR ) investigates the role of the CaSR in cancer and cardiovascular diseases in seven European laboratories.

The researchers are investigating the contribution of CaSR signalling to cell proliferation and differentiation and defining its function in vascular calcification. The ultimate objective is to model major signalling routes and controlling proteins for CaSR-dependent signal transduction.

Eleven young researchers (one ER and 10 ESRs) are working on individual projects. All ESRs are enrolled in PhD programmes where they attend project-specific training events. The 11 Fellows have received 23 awards and had 53 oral or poster presentations until now.

The first joint paper about CaSR signalling in physiology and cancer has been published in December 2012. 14 further scientific publications were authored by the Multifaceted CaSR Fellows and several other manuscripts are in preparation.

Development of the first systems biology model resulted in creation and uploading of the preliminary working version. The team updates the model regularly, based on MULTIFACETED CaSR data.

Partners of the project identified several research areas where work will continue after finishing the MULTIFACETED CaSR programme.

The first International CaSR Symposium has been organised in Vienna (1/12/2012) and was considered a great success by the participants from Europe, USA, Canada, Australia, and South America. Participants required the continuation of this event. A second CaSR Symposium will be organised in 2015. During the first international symposium on the CaSR, several promising collaborations were initiated with groups working in Europe, the USA, and Australia.