Investigation of an uncharacterised, embryonically lethal gene in immune cell development

"Animals develop from a single cell to an organism that can contain potentially trillions of cells, a feat of biochemical choreography made more remarkable by how rarely it goes wrong. One part of this sequence is the formation of the immune system, which keeps the animal healthy despite being currently exposed to pathogens. We study the development and function of one type of immune cells, known as T cells, that are an essential part of the adaptive, or learned immune response, including in humans. Whilst studying how immature T cells develop, we have identified a protein named TMEM131 that might be important for this development to proceed. Intriguingly, there is almost nothing known about what the function of this protein is, but crucially it is found in organisms from worms to humans, suggesting that it plays an important part in the development in many species. We also have evidence that TMEM131 plays a role more broadly in embryo development.
The main goal of this proposed research is to begin uncovering the function of TMEM131 at the molecular level. Our hypothesis is that TMEM131 is a protein chaperone, which means that it helps other proteins correctly fold into their 3-dimensional shape. Without this help, other proteins that are important in development may misfold and so will not function correctly. We believe TMEM131 helps an important protein complex in T cell development called the pre TCR to form efficiently.
We will use a variety of biochemical and cell biological techniques to provide the first molecular details for the function of TMEM131, which is predicted to be a large protein that is anchored into the internal membranes of cells. We will explore where in mammalian cells it is expressed and the topology of how it organised within these membranes, since this will indicate what it might interact with and when. We will also use the zebrafish model organism to find how the loss of TMEM131 expression disrupts embryogenesis more generally."