When a new pathogen, like a virus or bacteria is encountered, the immune system first has to recognise it and then produce enough targeted immune cells to effectively eliminate it. After the infection has resolved, many of the specific cells die because they aren’t needed anymore, but some of them persist long-term. Importantly, these cells can still recognise that pathogen and protect against the same infection in future, so this is called the memory response. Some memory cells can circulate throughout the body; this is how vaccines given in the arm can protect against many types of infections in different areas of the body. Recently, a new type of memory cell was discovered, and unlike circulating memory cells, these resident memory cells remain at the site of infection. Resident memory cells can form in almost any organ, including front line tissues like the skin and gut, so they are in an ideal position to defend against previously encountered pathogens. Our group is investigating which instructions these cells receive that allow them to stay in the tissue. As genes are essentially instruction manuals for cells, we have been studying which specific genes play a role in the development of these cells. We have been looking at the function of two genes called Hobit and T-bet. We have found that the Hobit gene is necessary for the development of resident memory cells in all organs. However, we found that the T-bet is only required for resident memory cell development in some organs. Research groups around the world are now targeting resident memory cells to generate better vaccines and treatments for certain cancers and autoimmune diseases. Our work shows that resident memory cells should to be studied in multiple organs to make these vaccines and treatments effective and to limit potential side-effects.