Telomeres are the very tips of chromosomes and have been studied intensely for their role in the replicative capacity of cancer and stem cells. In higher organisms, the telomeres of sperm and egg are longer than those of other cells, which have led to the hypothesis that lengthening of telomeres in germ cells is needed to reset the biological clock with every generation. Microbes that have a variety of different cell types provide a tractable means to address the question of telomere length in sex cells. Furthermore, such a group of microbes, the filamentous fungi, are among the species with the shortest telomeres known. One limitation of further studying these fungi is that one of the fundamental genes in telomere synthesis has yet to be identified. This gene encodes the telomerase RNA, which provides the template for synthesizing telomeres and is therefore crucial for life. Since telomerase RNA genes are highly divergent, with almost no sequence identity between organisms, they are much harder to identify than other genes in a new group of organisms. This project describes experiments to identify the first telomerase RNA in a group of microbes, the filamentous fungi. The experiments will take advantage of a long telomere repeat sequence, fortuitously present in a filamentous fungus of food microbiology, to devise a cross-disciplinary approach utilizing bioinformatics and molecular genetics. The length of the telomere repeat sequence means that the number of possible gene candidates will be reduced. Identifying the first telomerase RNA gene sequence within a diverse group of filamentous fungi will ultimately lead to a better understanding of telomere length regulation in sex cells and other cells, interactions between the telomerase RNA and essential proteins, and the evolution of this highly divergent gene.
Broader Impacts: Although this project is focused on gaining a better understanding of the role of telomeres in cell development, there are many outcomes that will benefit the broader scientific community. First, undergraduates will develop new tools, such as a novel telomere diagnostic assay, providing scientists in other laboratories with an easier way to study telomere length. This assay will be disseminated to the scientific community in the form of a peer-reviewed publication with undergraduate coauthors. Second, undergraduates will collaborate with scientists from around the world. Finally, the results of the research extend well beyond the molecular scope of this laboratory. For example, identification of the telomerase RNA gene from a new group of organisms, the filamentous fungi, will provide data that is of interest to evolutionary biologists and other scientists. Thus, undergraduates who have had such a broad exposure to research will continue in their careers by making more educated decisions.
