Periodic Reporting for period 1 - HoloCellDeath (Origins and evolution of programmed cell death machinery during the emergence of animal multicellularity)
Reporting period: 2018-03-01 to 2020-02-29
Regulated cell death is a process in which specific cells die in a genetically controlled way. It is essential in animals: both to replace damaged or infected cells, and as a part of normal development. As a result, understanding regulated cell death is an important step toward finding out how multicellular animals first evolved from their single-celled ancestors. This improves our basic understanding of our own past evolution, and of the factors that led to a process that's a critical factor in cancer and developmental biology today.
My objectives with this project were to find out when each protein component evolved; whether any of these components evolved before animals did, in the single-celled animals of ancestors; and what their functions might have been in these single-celled ancestors.
My objectives with this project were to find out when each protein component evolved; whether any of these components evolved before animals did, in the single-celled animals of ancestors; and what their functions might have been in these single-celled ancestors.
I performed a broad survey of the genomes of animals and their single-celled close relatives, searching for genes encoding proteins or protein domains that in animals play a part in regulated cell death. I found that the major elements of the best-known regulated cell death pathways, apoptosis, emerged at the onset of animals; but that some accessory proteins that are now involved in regulated cell death were already present before the origin of animals, in their single-celled ancestors. These include downstream effectors of apoptosis, inhibitors of apoptosis, and elements of caspase-independent regulated cell death pathways. It is possible that these genes had a different function in the single-celled ancestors of animals, and that they underwent a change of function ('functional cooption') as animals arose. Alternatively, it's possible that single-celled ancestors of animals already had simple forms of regulated cell death, perhaps protecting against the spread of infection through a population. Using cutting-edge genetic tools developed in the Multicellgenome lab, I am studying how some key genes behave when they are manipulated in single-celled relatives of animals, to understand what their original functions may have been in the single-celled ancestors of animals, and what changes they may have undergone as animals evolved.
I produced a survey of regulated cell death proteins across a larger number of organisms than was previously possible, especially among single-celled close relatives of animals living today. My work improved our understanding of the process in general by producing insights into the evolutionary timing of regulated-cell death proteins, and showed unexpectedly early origins of some of the proteins involved, as well as highlighting the crucial role that regulated cell death had in the origins and early evolution of animals.
Taking advantage of genetic manipulation possibilities newly available in a range of single-celled close relatives of animals, my ongoing work is examining the functions of some of these proteins. From this information, the scientific community will for the first time be able to draw conclusions about what these proteins might have been doing in the single-celled ancestors of animals.
Taking advantage of genetic manipulation possibilities newly available in a range of single-celled close relatives of animals, my ongoing work is examining the functions of some of these proteins. From this information, the scientific community will for the first time be able to draw conclusions about what these proteins might have been doing in the single-celled ancestors of animals.