Funding outcome

The level of calcium in the blood is tightly regulated, in oreder to prevent a myriad of symptoms from seizures to bleeding disorders. Central to this, parathyroid hormone (PTH) is secreted in response to low blood calcium levels. The signal for this occurs through blood calcium no longer binding to its receptor, a protein on cells called the calcium sensing receptor (CaSR). Consequently, the occurrence of low blood calcium levels when blood PTH levels are also low is a rarity. When this occurs in children it typically causes seizures and is always associated with abnormalities in the production of PTH or CaSR signaling. Dr. Alexander has identified a new protein that is mutated in a child with both low blood calcium levels and low PTH. The protein is called FAM111A. We know almost nothing about this protein. The objective of this project is therefore to determine the role of FAM111A in regulating the production and release of parathyroid hormone in response to low blood calcium levels. To accomplish this, cells containing the calcium sensing receptor that can release parathyroid hormone in response to altered calcium levels will be used. Wild type and or the mutant FAM111A will be added and/or manipulated in these cells to examine CaSR signalling and subsequent parathyroid hormone release. This work will help to establish how mutations in the FAM111A gene cause low calcium levels and low blood PTH. This knowledge will contribute to both our understanding of this rare childhood clinical disorder, but more importantly to calcium homeostasis in general, perhaps opening up new therapeutic targets for diseases of altered calcium homeostasis such as kidney stones and osteoporosis.