WEBVTT

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Hi, my name is Michelle
Sharif, and I am a junior

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at Mount Holyoke college.

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I am majoring in neuroscience
and minoring in studio art.

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Today I am going to talk to
you about my summer research,

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and what it takes to carry
out an independent project

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from start to finish.

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I spent my summer researching
on Alzheimer's disease in Carr,

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which is located on the
first floor of Kendade.

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Alzheimer's disease is a
progressive, degenerative, and

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incurable neurological
disease that

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causes deterioration of brain
cells and ultimately death.

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The disease is named after
Dr. Alois Alzheimer, who

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in 1906 noticed
changes in the brain

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tissue of a 56-year-old
woman who died

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of an unusual mental illness.

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Her symptoms included memory
loss, language problems,

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and unpredictable behavior.

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After she died, he
examined her brain

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and found many abnormal
clumps, which are now

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called amyloid plaques, and
tangled bundles of fiber,

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now called neurofibrillary,
or tau, tangles.

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The number of people
with Alzheimer's disease

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is expected to almost
triple from 4.5 million

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in 2000 to 13.2 million in 2050.

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It accounts for about
80% of dementia patients,

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characterized by increasing
memory loss, disorientation,

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difficulty speaking and
behavioral problems.

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Currently there are no cures for
AD, But treatments for symptoms

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are available, and
research continues.

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In order to investigate the
prevention and treatment

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of this disease, it is
important to understand

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the pathology of AD.

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In humans, AD is
characterized by two

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key pathological hallmarks,
being plaques and tangles.

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Beta amyloid
plaques are composed

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of beta amyloid precursor
protein which are built up

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in spaces between nerve cells.

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This disrupts the
communication between cells

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and the rest of the body.

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NFTs are composed of the
hyperphosphorylated protein

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tau, and they build
up inside cells.

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So what's tau?

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In its normal state, tau is
a microtubule binding protein

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that contains many
phosphorylation sites.

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In disease states, tau can be
excessively phosphorylated,

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thus unabling it to
bind to microtubules.

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It detaches and is
hyperphosphorylated

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and forms an oligomer.

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The sticky tau oligomers can
start to aggregate and form

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dimers composed of two
tau proteins, which

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eventually aggregate into NFTs.

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Although the exact mechanism
of toxicity is unknown,

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hyperphosphorylated
tau has been shown

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to have a significant role
in disease pathogenesis.

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To date however, there
have been very few studies

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that have explored the effect
of environmental enrichment

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on tau toxicity,
which is what I did.

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Environmental
enrichment-- research

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in the field of
neuroscience has proven

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that human brains
continue to be plastic

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long after development,
and throughout the entirety

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of life.

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Environmental enrichment has
shown to increase plasticity

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in the areas of brain associated
with learning and memory.

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Thanks to Thomas, who is
the Mount Holyoke College

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machinist, he was able to
build these chambers which

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is what I carried my study in.

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For those of you
who do not know,

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this is what a drosophila looks
like, and this was our subject.

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The advantages of
using a drosophila

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was that it has
a short lifespan,

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the tau protein is
homologous to one in humans,

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and it is relatively easy
to manipulate the fly.

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We used a GAL4/UAS
system which was in order

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to facilitate the expression
of the mutated tau

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protein in the fly.

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So my research-- My research
looked at studying tau toxicity

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in neurons using wild-type tau.

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The tau NFTs are more
prevalent in neurons,

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and research shows that
wild-type tau protein

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is axonally transferred from
the ventral hippocampus neurons

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to connect its
secondary neurons.

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I conducted two studies, a
10-day and a lifespan, however,

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the lifespan is still
ongoing, and is at 58 days.

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The 10-day comprised of flies
which were aged for 10 days,

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kept at 25 degrees
Celsius, and every two

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days I would count the number
of dead flies, change the food,

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and I would make sure that any
dead flies were noted down.

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Flies were then frozen
at -80 degrees Celsius.

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And I will now perform
a Western blot in order

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to quantify my results.

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Here's an overview of my method.

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I basically
collected the stocks.

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I then [? burdened ?] the
flies, set up my crosses,

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and then sorted my progeny,
selecting against the stubble,

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curly-winged, and white-eyed.

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What does it take to carry
out an independent project?

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The advantages were that
I was able to develop

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knowledge and skills in
my area of discipline.

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I had a greater sense
of competence attributed

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to completing a
large scale project,

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and I had an experience of
being in a professional role.

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Challenges were
being persistent.

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Things did not always
work how I wanted them to,

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and I had to keep on trying.

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And living in South
Hadley over the summer

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was extremely
difficult. My next steps

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are carrying out a
Western blot, waiting

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for my last couple of
flies to expire, and run

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different assays to
test cognitive function.

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Here is an overview of my
summer, and just as a closing.

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So this is what we do
during our practices.

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[INAUDIBLE] Yeah.

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That's good.

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Thank you.

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