Using mini-brains to see how brain cells are affected by altered NF-kB

Summary

We are interested in a molecular pathway called the NF-kB pathway that is present in cells throughout the body and controls many basic functions of cells. However, the NF-kB pathway doesn't operate in the same way in all types of cells. In immune cells, activating the NF-kB pathway causes inflammation. In contrast, in brain cells, activating the NF-kB pathway appears to be beneficial, allowing the formation of new memories as well as protecting nerve cells from damage.

We have previously found that people with MS have a lower-than-normal level of a molecule, called IkB-a, that blocks the NF-kB pathway. This means that immune cells in people with MS tend to be more activated and inflammatory than those in other people.

Currently, there is nothing known about how the lower-than-normal levels of IkB-a seen in people with MS might affect the cells in the brain. A complicating factor in studying this is that we cannot study pieces of people's brains to look at the effects of low levels of IkB-a. Therefore, we will explore whether we can use a type of stem cell called an induced pluripotent stem cell (iPSC) to produce brain cells and brain organoids (mini brains in a dish) that can be used to look at the effects of low levels of IkB-a in brain cells.