Investigating the function of SLC15A3: a promising gene linked to Alzheimer's disease

Alzheimer's disease (AD) is a progressive condition in the brain whereby there is accumulation of misfolded proteins, leading to the loss of neurons and their connections. Many genes associated with the risk of developing AD are implicated in microglial function. Microglia are immune cells which reside in the brain and are responsible for the clearance of harmful stimuli. In AD, they are activated for sustained periods which can lead to chronic neuroinflammation and contribute to disease pathology. When investigating microglial genes, the SLC family was identified as having a very high predictive value for AD development. This family of proteins has been shown to be important for coordinating immune responses and regulating inflammation systemically, suggesting that the gene may play a role in the immune response in the brain by regulating microglial function. In this project, we will compare the expression of genes from the SLC family in non-diseased and AD human brains using published databases, while investigating other genes belonging to the same gene family with similar functions. We will also use human tissue to confirm that these proteins are expressed in microglial cells. Subsequently, we will use human cells which can be differentiated into microglial-like cells to create a cellular model which mimics the presence of misfolded proteins. Then we will induce gene knockouts to study the function of our genes of interest in a human AD model. Hence, we will characterise expression and function of these genes to understand how the genetic variants may contribute to chronic neuroinflammation and AD pathology.