My Research Topic
As a young scientist-in-training, I have come to appreciate the many fields of research that are currently taking place. Any protein can be studied in a number of disciplines, from behavioral biology, to molecular genetics, and to biophysics. Since one scientist can’t possibly undertake the whole research, many other colleagues are involved and thus bringing different perspectives to the table of discussion, as well as commiserating with each other on the failures and “strange” data. While I can’t discuss the details of my research, I can give background information and its relevance. This might actually be more informative since the details of my study might bore most of you.
Currently, I am studying endoplasmic reticulum (ER) stress because ER stress initiates either cytoprotective mechanisms or dire physiological consequences such as cell cycle arrest and cell death. ER functions include folding and packaging newly synthesized proteins and it is also the site of protein quality control where misfolded proteins are retained. Understanding how cells cope with ER stress can elucidate ways to maintain cell viability. More importantly, ER stress is associated with many diseases, such as Alzheimer’s and Huntington’s disease. Of course, in the diseases mentioned, ER stress is not the only underlining cause of pathology. Rather, many malfunctions contribute to the overall etiology of the disease. I should state now that cell cycle arrest and/or cell death are important aspects of cells and that they are often more good than bad for the cells. There are actually two types of cell death, apoptosis and necrosis. I’ll blog about apoptosis later, but necrosis is perhaps the worse of the two. Cell cycle arrest usually indicates some form of activated checkpoint response. In other words, cells are capable of regulating themselves.
And ER stress is just one of these regulating mechanisms. It was first talked about around the late 70’s when a protein was found to be highly expressed under certain stress conditions. Later as more work was done on this protein, a pathway was beginning to emerge about how cells cope with ER stress. What is ER stress? In basic terms, ER stress is caused by the disruption of the ER folding machinery that affects protein maturation and causes accumulation of unfolded proteins within the ER lumen. In experimental conditions, we can induce ER stress by adding chemicals or drugs that would affect proper protein folding, or by disrupting the calcium stores within the ER lumen. Calcium, which will be a topic of a future blog, is an essential second messenger in the cell (all of you are probably more aware the calcium is good for the bones). Cells keep calcium ion concentration under tight control since excess free flowing calcium is toxic to a cell. I digress. There are two distinct features as a result of ER stress: a transient stop in protein translation and an increase in mRNA expression of certain proteins. Presumably, the inhibition in protein translation will help reduce the amount of newly synthesized proteins in the ER, and the increase in certain proteins can help facilitate the folding and or trafficking of the accumulated proteins. Interestingly, apoptotic genes are also upregulated during ER stress. Exactly how cells choose cytoprotective mechanism or apoptotic pathway is not yet understood.
My project involves the study of one of these upregulated proteins. So far, no known function has been discovered; however, its amino acid sequence is well conserved across human, mouse, and rat (near 97% homology). My job is to find out where this protein is localized in the cell and to determine what its role is in ER stress. The working hypothesis is that this protein is beneficial to the cells; I think that would make a better story. Of course, I have very little data that support that hypothesis. Currently, I am trying to design and make molecular tools that would aid me in my endeavor, tools such as antibody and recombinant fusion protein. It is an exciting project. It is my project.
As a young scientist-in-training, I have come to appreciate the many fields of research that are currently taking place. Any protein can be studied in a number of disciplines, from behavioral biology, to molecular genetics, and to biophysics. Since one scientist can’t possibly undertake the whole research, many other colleagues are involved and thus bringing different perspectives to the table of discussion, as well as commiserating with each other on the failures and “strange” data. While I can’t discuss the details of my research, I can give background information and its relevance. This might actually be more informative since the details of my study might bore most of you.
Currently, I am studying endoplasmic reticulum (ER) stress because ER stress initiates either cytoprotective mechanisms or dire physiological consequences such as cell cycle arrest and cell death. ER functions include folding and packaging newly synthesized proteins and it is also the site of protein quality control where misfolded proteins are retained. Understanding how cells cope with ER stress can elucidate ways to maintain cell viability. More importantly, ER stress is associated with many diseases, such as Alzheimer’s and Huntington’s disease. Of course, in the diseases mentioned, ER stress is not the only underlining cause of pathology. Rather, many malfunctions contribute to the overall etiology of the disease. I should state now that cell cycle arrest and/or cell death are important aspects of cells and that they are often more good than bad for the cells. There are actually two types of cell death, apoptosis and necrosis. I’ll blog about apoptosis later, but necrosis is perhaps the worse of the two. Cell cycle arrest usually indicates some form of activated checkpoint response. In other words, cells are capable of regulating themselves.
And ER stress is just one of these regulating mechanisms. It was first talked about around the late 70’s when a protein was found to be highly expressed under certain stress conditions. Later as more work was done on this protein, a pathway was beginning to emerge about how cells cope with ER stress. What is ER stress? In basic terms, ER stress is caused by the disruption of the ER folding machinery that affects protein maturation and causes accumulation of unfolded proteins within the ER lumen. In experimental conditions, we can induce ER stress by adding chemicals or drugs that would affect proper protein folding, or by disrupting the calcium stores within the ER lumen. Calcium, which will be a topic of a future blog, is an essential second messenger in the cell (all of you are probably more aware the calcium is good for the bones). Cells keep calcium ion concentration under tight control since excess free flowing calcium is toxic to a cell. I digress. There are two distinct features as a result of ER stress: a transient stop in protein translation and an increase in mRNA expression of certain proteins. Presumably, the inhibition in protein translation will help reduce the amount of newly synthesized proteins in the ER, and the increase in certain proteins can help facilitate the folding and or trafficking of the accumulated proteins. Interestingly, apoptotic genes are also upregulated during ER stress. Exactly how cells choose cytoprotective mechanism or apoptotic pathway is not yet understood.
My project involves the study of one of these upregulated proteins. So far, no known function has been discovered; however, its amino acid sequence is well conserved across human, mouse, and rat (near 97% homology). My job is to find out where this protein is localized in the cell and to determine what its role is in ER stress. The working hypothesis is that this protein is beneficial to the cells; I think that would make a better story. Of course, I have very little data that support that hypothesis. Currently, I am trying to design and make molecular tools that would aid me in my endeavor, tools such as antibody and recombinant fusion protein. It is an exciting project. It is my project.
