Project 467213

SARS-CoV-2 the respiratory virus responsible for millions of deaths around the world since its first appearance in 2019 , in Wuhan, China. Despite the high vaccination rates, the danger of COVID-19 persists, especially due to the variants (e.g. omicron) that are emerging by the mutation of the virus. The damage to the lungs which is responsible for increasing the severity of disease is attributed to our immune system that overreacts to infection. One of the associated cell types is macrophages , which survey the tissue to engulf any foreign entity, like a virus, and release inflammatory signals. The extent of this release depends on the patient genetics, which serves as a prompt to study the host response closely. One striking and overlooked aspect of COVID-19 is its effects on the nervous system. Commonly, the loss of sense of smell and taste and other neurological symptoms, such as muscle aches, headaches and occasional loss of consciousness suggest that there is a contribution of the brain in the clinical presentation of COVID-19.We aim to study the role of microglia , the macrophages of the brain , in brain inflammation and neuronal damage in response to SARS-CoV-2 infection. Since microglia exert their proper function in a three-dimensional network, our lab will use human stem cells which have the ability to generate neurons and their supporting cells (oligodendrocytes, astrocytes) in a small spheroid that simulates the brain. In addition, we will manipulate the genes that are expressed by microglia using a genome editing technology called CRISPR-Cas9. This controlled environment allows us to quantify the levels of virus in each cell type, the inflammatory factors released by microglia and the damage they induce in neurons with and without gene editing.