Dear supervised exploration. I have discovered that

Dr. Raveill and the Biology Search Committee:


I am writing to
apply for the Assistant Professor position (#998225, #998223) in Biology at the
University of Central Missouri, as advertised on the University of Central
Missouri website. I am currently a Senior Research Scientist at the University
of Missouri – Kansas City School of Medicine. I am confident that my research
interests and teaching experience make me an ideal candidate for your open

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indicated on my curriculum vitae, I received my undergraduate degree in biology
from a small liberal arts college in the State of Washington, and from there
received my graduate degrees in biology at Kansas State University. Having
spent time at both private and public institutions – one primarily focused on
teaching and the other a research-focused institute – I desire to work at an institution
where I can incorporate both aspects. I value the education, mentorship, and
outside learning opportunities provided to students at a university like
University of Central Missouri, and I would be honored to be part of the UCM
community (where my wife Chrislyn (Johnson) Means graduated with her
undergraduate and graduate degrees in biology).


have a diverse teaching record that started in graduate school when I taught
the introductory biology course, Principles of Biology. From there I have
taught both undergraduate and graduate courses, as well as lab sections as
small as 12 students and lecture sections as large as 60. One
of my roles as a teacher is to assist in the learning of facts and key concepts
to my students. When I recollect on my time in the classroom and the teachers
that inspired me, I remember the ones that motivated me to think critically and
to understand the material on a deeper level. I remember those that were
excited and passionate about what they did. I strive to be this kind of
teacher. I want to create an environment that rewards curiosity and allows for
supervised exploration. I have discovered that the amount of time that I put
into preparing translates to how students learn. I also try to identify how
students learn best as individuals and in groups, and I like to let the lesson
plan evolve as I interact with the students. My goal as an educator is to
communicate information, not to just memorize facts, but also to help students learn
how to think.


I believe that learning is an active process,
where my job as a teacher is to guide it. I work towards not only supplying information,
but providing the means to independently acquire knowledge and to supply ideas
in different situations. I strive to arouse students’ critical thinking skills
and intellectual growth and set the stage for lifelong learning opportunities.

Two essential factors to achieve this are my mastery of and perhaps more
importantly my enthusiasm for the material. While success partially depends on
each student, I believe students that are properly motivated and driven by
their own curiosity enjoy the learning process. One of my favorite parts of teaching is
helping a student that is struggling learn challenging material by adjusting my
approach to meet their needs. I enjoy creating new instructional strategies to
convey material – games, debates, guest speakers, and clickers are among my
favorite activities. I am prepared to teach introductory as well as upper level
courses. I am also very excited to develop new courses focused on neurobiology
with emphasis on neurodegeneration and cell death. My passion for biology is
due, in part, to my involvement in research at the undergraduate level. I look
forward to supervising students interested in the research process, as I have
mentored and trained scientists, high school outreach, undergraduate, graduate,
and medical students on various research projects in the lab.


My own research would be an important part of my teaching,
as it provides an example of the scientific process in action, performed by
someone the students know. In addition, I would try to incorporate my research
into the curricula of any laboratory courses I might teach. In graduate
courses, I would enjoy having students perform a semester long project based on
my research, whereas in upper division undergraduate courses, students could perform
mini-projects, again based on my research. I believe this approach, where
students perform actual experiments on a related topic, brings a sense of
ownership to their lab experience and results in a much deeper understanding.


My overall research goal is to understand the physiological
and pathological roles of proteins involved in neurodegeneration. In
particular, I want to understand the role of cell death proteins such as the caspase
proteases and the microtubule stabilizing proteins such as Tau in health and
disease. This would help identify new therapeutic targets, and possibly new
physiological roles for these proteins, to give us a better understanding of
what triggers the disease state. One way that I will address this is to dissect
out individual brains from drosophila or mice and stain them for markers of
neurodegeneration. In addition, I take these brains and process them to be able
to examine various proteins to determine changes from normal to the disease


Physiologically, Alzheimer’s disease (AD)
involves damage and eventual death to brain cells. It is a progressive and
irreversible neurodegenerative disorder with no known cure or clear
understanding of the mechanisms and molecular determinants involved in the
disease process. A majority of the destruction that occurs in AD takes
place in parts of the brain that are vital for memory, such as the cortex. The
disease is also characterized by more specific changes in the brain, including
the build up of plaques and tangles, made up of beta-amyloid protein and tau
protein, respectively. By the time symptoms of AD occur, these physiological
changes in the brain have already begun. Apart from memory deficits, AD
pathological symptoms involve impairments in regulation of various
physiological processes, including circadian regulations, sleep patterns and
hormonal secretion. As more cells in the brain die, the symptoms progress until
eventually the brain can no longer perform necessary functions such as
swallowing and breathing. As
a post-doctoral fellow, I identified a new regulator that linked cell death and
neurodegeneration with circadian regulation. Apoptosis is an important
physiological mechanism by which a single cell is eliminated from living
tissue. Since the process is mediated by specific proteins encoded in the
host’s genome, it is a programmed cell death. Apoptosis plays a critical role
during normal development and homeostasis of adult tissues. Consequently,
deregulation of apoptosis is commonly associated with diseases ranging from
cancer to neurodegeneration. In humans, aging is often associated with reduced
function of the circadian clock and increased incidence of neurodegeneration, but the mechanism that links reduced circadian function
and increased neurodegeneration is not known. Our
results suggest that the circadian kinase Casein Kinase I inhibits the
activation caspases to prevent Tau cleavage, and that the circadian clock
defects confer sensitivity to expression of active caspase in response to
prolonged light. We establish a link between the circadian clock factors, light,
cell death pathways and Tau toxicity. I continued my work on neurodegenerative
processes as a Senior Research Scientist using mammalian models. I provided the first evidence for a non-transgenic mammalian
model of tauopathies during normal aging. Normally aged mice that are not
genetically modified and have not been subjected to neuronal damage show
behavioral cognitive impairment and a high level of active caspase compared to
young animals of the same strain. In addition, we detected truncated Tau in aged
mice, which was most prominent in the forebrain. This increased level of caspase
activity and cleaved tau correlated to cognitive deficits associated with


Disruptions in calcium homeostasis
are implicated in disease processes and have become a major focus of study in multifactorial
neurodegenerative diseases such as AD. Calcium serves a vital role in the physiological functioning
of the central nervous system. One common element that presents with several features of AD
is disrupted neuronal calcium signaling. Increased intracellular calcium levels
are functionally linked to amyloid plaques, tau tangles and synaptic
dysfunction. Calcium overloading and
oxidative stress have been implicated in AD pathogenesis. In AD brains calcium
levels are abnormal and this leads to caspase activation and eventual Tau cleavage.

I am investigating the role that the calcium receptors have in disease onset
and progression. Initial data from our plate reader assays and whole brain and
single-cell calcium imaging show that overexpression of the calcium receptor,
IP3R exacerbated calcium overloading-induced neuronal apoptosis, which was
mediated by caspase-3 apoptotic pathway. In addition Tau associates with IP3R
and when Tau is added to neuronal cells an increase in intracellular calcium
likely from the activation of the ER-calcium IP3Rs is observed. There is
evidence for ER calcium stores dysfunction in AD. These abnormalities have been
related to beta amyloid pathology, but to our knowledge, the modulation of IP3R,
by Tau related pathology has not been reported before. Our results suggest that
downregulating IP3R expression or regulating caspase activity in neurons could
be beneficial to AD patients.


Some important questions that still need to be addressed
concern the time frame in which such ionic dyshomeostasis occurs in AD: Does the ionic deregulation precede or
follow the onset of the pathology? Is this a cause or a consequence of the
disease? Discovering the physiological consequences of regulating various
factors that can lead to neurodegeneration will help us unravel this complex
interaction that maintains homeostasis. In addition, I have a number
of candidate genes I identified in a screen for factors involved in neurodegeneration.

These will need further characterization and their roles in disease determined.

This can be done initially with relatively simple assays allowing for
undergraduate and graduate students to be involved from the beginning.


background in liberal arts education, passion for teaching, and interest in
collaborative research would be an asset to the biology program at UCM. I
believe the environment at UCM would enable me to flourish professionally and
personally, and I look forward to visiting with you to discuss
this exciting opportunity in more detail. I am
confident that my research interests and experience combined with my teaching
skills make me an excellent candidate for the Assistant Professor of Biology
position at UCM. Thank you for your time and
consideration. I have attached my CV. Feel free to contact me with any
questions at [email protected] or by phone at 660-232-2044.