Background
What is ALS?
Amyotrophic lateral sclerosis, or ALS, is a complex autoimmune disease that removes the ability for the nerve cells of the body to properly interact with the muscles of the body. Due to this, the nerve cells become damaged and die. This disease typically affects those between the ages of 50 through 60, but it can occur much earlier or later in life. The early stages usually begin with slurred speech and increased clumsiness and further loss in motor capabilities progresses in a short period of time. Currently, there is no cure for ALS, and most die as a result of the disease within 3 to 5 years.
What is our goal?
Our goal is to find out more about the different systems that play a part in ALS by researching specific genes encoding some of these pathways in drosophila melanogaster. These model organisms are an excellent tool for studying diseases since they have nearly as many genes as we do and about 65% of human-related diseases have a related homolog in these flies.
What genes are we studying?
SAFB
SAFB stands for Scaffold Attachment Factor B gene that is believed to be involved in regulation of alternative mRNA splicing, regulation of transcription, and is expressed in several structures, including the embryonic/larval central nervous system of an organism and the germline cell. It is predicted to play a role in enabling mRNA binding activity and sequence-specific DNA binding activity. SAFB proteins are highly expressed in the central nervous system and immune systems. If this protein were related to ALS, then one would see downregulation as there could be a loss of transcription in the nervous system, which can affect the motor neurons. However, there could also be overexpression - too many proteins for the nervous system, which causes upregulation in relation to ALS.
VPS39
VPS39 Encodes a subunit of the HOPS complex that is required for autophagosome maturation. This gene is specifically involved in binding to membrane-anchored small GTPases. In order to understand the importance of VPS39 it is also important to know that autophagosomes use lysosomes in the cell to degrade cytosolic components in the cell such as proteins and organelles. Thus, we suspect that a down regulation of this protein likely leads to a decrease in the production of autophagosome formation and cause massive neuronal death. The inability for the autophagosome to degrade agitated and ubiquitinated proteins can lead to synaptic impairment, damage to the organelles, and cell death in the central nervous system
DSH
DVL stands for disheveled gene, where one of the three DVL genes found in humans, DVL3, is very similar to the Drosophila disheveled gene, dsh. Dsh is necessary for establishing polarized cell and segment arrays that are coherent in embryos and plays a part in wingless (wg or wnt) signaling, potentially by allowing target cells to receive the wg signal and then redistributing arm protein in response to the signal in developing organisms. Wnt signaling is the collective name for the chemical signaling pathways in which the proteins made by these genes participate. It appears that wg signal is necessary to establish the polarity and identity of planar cells. In our case, in response to ALS, dsh effects Wnt signaling by either up or down-regulation depending on the particular DVL gene, which has been demonstrated to be altered or involved in the pathophysiology of ALS.
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