Hi, my name is Michelle Sharif, and I am a junior at Mount Holyoke college. I am majoring in neuroscience and minoring in studio art. Today I am going to talk to you about my summer research, and what it takes to carry out an independent project from start to finish. I spent my summer researching on Alzheimer's disease in Carr, which is located on the first floor of Kendade. 

Alzheimer's disease is a progressive, degenerative, and incurable neurological disease that causes deterioration of brain cells and ultimately death. The disease is named after Dr. Alois Alzheimer, who in 1906 noticed changes in the brain tissue of a 56-year-old woman who died of an unusual mental illness. Her symptoms included memory loss, language problems, and unpredictable behavior. After she died, he examined her brain and found many abnormal clumps, which are now called amyloid plaques, and tangled bundles of fiber, now called neurofibrillary, or tau, tangles. 

The number of people with Alzheimer's disease is expected to almost triple from 4.5 million in 2000 to 13.2 million in 2050. It accounts for about 80% of dementia patients, characterized by increasing memory loss, disorientation, difficulty speaking and behavioral problems. Currently there are no cures for AD, But treatments for symptoms are available, and research continues. 

In order to investigate the prevention and treatment of this disease, it is important to understand the pathology of AD. In humans, AD is characterized by two key pathological hallmarks, being plaques and tangles. Beta amyloid plaques are composed of beta amyloid precursor protein which are built up in spaces between nerve cells. This disrupts the communication between cells and the rest of the body. NFTs are composed of the hyperphosphorylated protein tau, and they build up inside cells. 

So what's tau? In its normal state, tau is a microtubule binding protein that contains many phosphorylation sites. In disease states, tau can be excessively phosphorylated, thus unabling it to bind to microtubules. It detaches and is hyperphosphorylated and forms an oligomer. The sticky tau oligomers can start to aggregate and form dimers composed of two tau proteins, which eventually aggregate into NFTs. Although the exact mechanism of toxicity is unknown, hyperphosphorylated tau has been shown to have a significant role in disease pathogenesis. To date however, there have been very few studies that have explored the effect of environmental enrichment on tau toxicity, which is what I did. 

Environmental enrichment-- research in the field of neuroscience has proven that human brains continue to be plastic long after development, and throughout the entirety of life. Environmental enrichment has shown to increase plasticity in the areas of brain associated with learning and memory. Thanks to Thomas, who is the Mount Holyoke College machinist, he was able to build these chambers which is what I carried my study in. 

For those of you who do not know, this is what a drosophila looks like, and this was our subject. The advantages of using a drosophila was that it has a short lifespan, the tau protein is homologous to one in humans, and it is relatively easy to manipulate the fly. We used a GAL4/UAS system which was in order to facilitate the expression of the mutated tau protein in the fly. 

So my research-- My research looked at studying tau toxicity in neurons using wild-type tau. The tau NFTs are more prevalent in neurons, and research shows that wild-type tau protein is axonally transferred from the ventral hippocampus neurons to connect its secondary neurons. 

I conducted two studies, a 10-day and a lifespan, however, the lifespan is still ongoing, and is at 58 days. The 10-day comprised of flies which were aged for 10 days, kept at 25 degrees Celsius, and every two days I would count the number of dead flies, change the food, and I would make sure that any dead flies were noted down. Flies were then frozen at -80 degrees Celsius. And I will now perform a Western blot in order to quantify my results. 

Here's an overview of my method. I basically collected the stocks. I then [? burdened ?] the flies, set up my crosses, and then sorted my progeny, selecting against the stubble, curly-winged, and white-eyed. 

What does it take to carry out an independent project? The advantages were that I was able to develop knowledge and skills in my area of discipline. I had a greater sense of competence attributed to completing a large scale project, and I had an experience of being in a professional role. Challenges were being persistent. Things did not always work how I wanted them to, and I had to keep on trying. And living in South Hadley over the summer was extremely difficult. My next steps are carrying out a Western blot, waiting for my last couple of flies to expire, and run different assays to test cognitive function. 

Here is an overview of my summer, and just as a closing. So this is what we do during our practices. [INAUDIBLE] Yeah. That's good. Thank you.