Grant: Discovery Grants Program - Individual

Ribosomes are tiny molecular machines that are present by the hundreds of thousands in all cells. They play an essential role in every aspect of life, as they are the link between the genome (or DNA) and proteins. Ribosomes read genetic information and translate it into the corresponding protein. In turn, proteins provide the cell with architectural and structural support, the ability to move (such as muscle contraction), and often themselves act as miniature molecular motors in providing the cell with the ability to use energy, to grow, and to divide. These are all key aspects to the normal day-to-day life of a cell. We have an increasingly sophisticated understanding of how ribosomes read genetic material and assemble the corresponding protein, much like we understand well the internal combustion motor of a car. The research proposed here looks at how the ribosome is assembled and at another miniature molecular machine, called the SSU processome, which assembles part of the ribosome. That is akin to my saying that my interests are in how cars are assembled and how car assembly lines work.*Ribosomes are assembled from a special type of genetic material called ribosomal RNA and also contain many proteins. The ribosomal RNA has to be made and cut, and is at the same time assembled with proteins to give a mature ribosome. The proposed Specific Aim 1 looks at mechanisms by which ribosomal RNA is made, cut and assembled at the same time instead of as separate events. Using the car assembly analogy, this is akin to assembling a car from pieces that are themselves unfinished.*Throughout the very complicated process of ribosome assembly are numerous steps that must be monitored. This is typically done, as proposed in Specific Aim 2, by the addition of a small chemical, called a phosphate group, to proteins working on assembling ribosomes. This phosphate group turns these proteins on or off. Referring to our car assembly line model, this is akin to assembling cars faster or slower, or telling the workers to put more paint or less paint on the car.*This work has the potential to greatly benefit all Canadians. Ribosome assembly is a key fundamental process in all cells. It influences all of biology, from ecology to human health (think all cancers and many genetic disorders) to crop production and livestock in agriculture. I anticipate that this research will allow us to better understand the many steps in the complicated process of ribosome assembly. In turn, this may allow us to manipulate ribosome assembly to increase crop and livestock production and also to intervene when ribosome assembly becomes defective.