Download Cellular and Molecular Biology (HTH SCI 1I06) Legacy Summary

Cellular and Molecular Biology (HTH SCI 1I06)
Legacy Summary
Group Name: Robertson-2
Date: November 29, 2012
Group Members:
Annelise Kohler
Dorna Ravamehr
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Herman Bami
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Nayantara Ghosh
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Ramya Kancherla
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Samir Nazarali
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Welcome, BHSc Class of 2017! We’re delighted to have you join us in this amazing faculty
for the next four years! One of the courses that you will be taking next year is Cellular and Molecular
Biology (HTH SCI 1I06) and we would like to present to you what we think are the most important
aspects of this course. Having taken this course ourselves, we hope this FAQ sheet provides you with
a more extensive understanding of what it is all about and contributes to your success in first year!
Good luck!
What is Cellular and Molecular Biology?
Cell Bio is a specialized biology course for first year students in the faculty of Health
Sciences. This course exclusively focuses on cellular communication, as well as research being
conducted in the field of molecular biology. It is taught by two professors: Dr. Eric Seidlitz on
Tuesdays (call him Eric!) and Dr. P.K. Rangachari on Thursdays (call him Chari!), who focus on
intra-cellular communication and intercellular signaling respectively.
What do you learn in Eric’s Tuesday lectures?
Tuesday’s lectures focus on the processes involved in gene expression from DNA to protein.
You will see that these proteins can act as receptors for signaling molecules. An easy way to think of
this concept is to understand that the proteins produced, in the processes we learn about in Tuesday’s
lectures, are used in the intercellular signaling discussed in Thursday’s lectures.
The course begins with an introduction to DNA, which is present in all living organisms and
is composed of a sugar-phosphate backbone. It exists in the form of antiparallel strands. In the
process of DNA replication, which is essential for cell division, these strands are unzipped and
synthesized in either one continuous strand, known as the leading strand, or in fragments, present in
the lagging strand. DNA is also used as a template for RNA transcription. During this process, RNA
is produced in a way analogous to DNA replication as it uses similar mechanisms. After transcription,
RNA translation is the next step in protein synthesis. Translation involves the building of an amino
acid chain from a modified version of the original RNA transcript (known as mRNA). In order to
accomplish this, the mRNA is transported from the nucleus to ribosomes (functional units that build
proteins) in the cytoplasm. This mRNA matches up with bases located on one end of transfer RNAs
(tRNAs). The other end of tRNA carries with it the amino acid that is being coded for. Polypeptides,
which are chains of amino acids, are formed in this ribosome and then travel to the endoplasmic
reticulum (ER), where further modifications take place. For example, a sugar group is added onto
one end of the polypeptide in a process referred to as N-linked glycosylation. The polypeptide is
then folded and transported to the Golgi body for continued modifications. Once a functional protein
is formed, it can be transported to wherever it is needed. This entire process follows the central
dogma of molecular biology as DNA is transcribed to RNA, which is subsequently translated into
polypeptides. However, research has shown there to be many exceptions to this, such as RNA being
reverse-transcribed into DNA.
Every step in this process of DNA to proteins is controllable and can be inhibited. However,
the earlier on in the process this occurs, the less energy that is used. Gene regulatory proteins can
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act to control gene expression during DNA interaction or pre-transcription. They can work in many
ways to either activate or repress the expression of a gene.
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What do you learn in Chari’s Thursday lectures?
Thursday lectures will focus more on signaling molecules. From these lectures, you will gain
an understanding of how signaling works as well as the historical approaches that allowed for the
study of these molecules. Signaling is the process of transmitting information between cells. The
most important idea that we took away from these lectures was that every signaling molecule has
certain general features. These are: synthesis, release, response and termination. The storage of
these molecules is not always necessary.
Three molecules that were studied in depth in this course were histamine, acetylcholine and
norepinephrine. All three molecules are stored within vesicles. The release of these molecules is
dependent on environmental conditions. For example, histamine can be released as a result of injury
or the presence of antigens (ex. peanut molecules in allergic reactions). Once released, these
signaling molecules bind to receptors in order to produce their respective effects.
Receptor proteins can be found on cell membranes, in the cytoplasm or in the nucleus. When
a signaling molecule, also known as a ligand, binds to a receptor, the receptor can direct the cell to
elicit a response - for example, synthesizing a protein. Another important part of this section of the
class is the examination of the Clark occupancy model, which attempts to explain the activity of
drugs when bound to receptors. In this model, it was suggested that the response of a drug is
proportional to the number of receptors occupied. However, this model was later modified and is
now called the modern receptor theory. This new model introduced the idea of spare receptors
(the ability of a ligand to produce a full response without occupying all of the receptors) and partial
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agonists (the inability of a ligand to produce a full response
even when all receptors are occupied). The model also
mentions other forms of agonism such as inverse agonism,
competitive antagonism and non-competitive antagonism.
The two types of receptors that were mentioned in this class
were ligand-gated ion channels and G-protein coupled
receptors. The former controls the flow of ions across a
membrane when a signaling molecule binds to it and the
latter triggers secondary messenger molecules, which initiate
an amplification process to produce an increased response.
An important second messenger molecule studied in this
course was cyclic adenosine monophosphate (cAMP).
cAMP, which is synthesized from ATP by the binding of a
ligand to a G-protein, is used to activate enzymes that
convert the chemical signal into a cellular response (signal
transduction).
By studying the effects of neurotoxins such as
sarin and atropine, on receptors within neurons, we can
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deals with messengers on demand, such as steroids and
prostaglandins. Although these are also signaling
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molecules, they are not stored like histamine,
norepinephrine and acetylcholine.
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How do these two parts tie together?
The most important understanding that you will gain from this class is that both components
of it have an inherent connection. The intercellular signals and pathways discussed in Thursday’s
lectures get transduced into intracellular signals that control gene expression, the focus of Tuesday’s
lectures. Also, the synthesis of all the receptors, enzymes and proteins involved in intercellular
signaling can be traced back to the creation of proteins from DNA. It is especially key to
remember that the concepts of synthesis, storage, release, response and termination, that can
be applied to intercellular signaling molecules, are just as applicable to gene expression, which
is intrinsically a form of communication. The understanding that both sections of the course are so
inextricably tied will aid you tremendously in the evaluations conducted in this class, such as
RAPSES (Rapid Problem Solving Exercises) and TRIPSES (Tri-Partite Problems Solving
Exercises). These will require creative thinking and the ability to link knowledge, presented in both
sections, to answer application questions based on real-life problems.
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What was the hardest part of this class?
The content presented in this class can be challenging at certain times, and we found
ourselves struggling the most with the types of agonism taught in Chari’s Thursday lectures. Most of
us had a very particular idea of what an agonist is and does - binding to a receptor molecule to
produce one type of response. We never knew that there are actually different types of agonists that
can produce varying responses within a cell. We were also unaware of the fact that receptors can
also differ in their functions. Some receptors can actually display constitutive activity, which means
that they produce a basal level of activity (i.e. induce a certain cellular response), even without the
presence of a ligand molecule.
Another really strange part about all of this is that different molecules present within a cell
can constantly interact with receptors, and actually cause them to undergo conformational (shape)
changes. Some of these random changes in shape stimulate the receptor to take on a more “active”
form. Full agonists are attracted to these active forms and can actually enhance the activity of a
receptor. However, not all receptors undergo this shape change, as they must exist in equilibrium
between their “active” and “inactive” forms. The binding of a full agonist to an active receptor
produces a drug-receptor complex, thereby decreasing the number of “active” receptors. Thus,
equilibrium is pushed to produce more “active” receptors, accelerating the response.
However, there are actually molecules, known as inverse agonists, which can bind to the
“inactive” form of a receptor. This produces an effect completely opposite to that of a full agonist!
Inverse agonists are not to be confused with antagonists, although they may seem similar. The
binding of a neutral antagonist (inhibits the binding of an agonist) to a constitutively active receptor
does not actually have an effect on the response produced by it. An inverse agonist, on the other hand,
actually binds to the “inactive” form of a receptor. This decreases the effective response of the
receptor to below basal level. Since it binds to the “inactive” form of the receptors (forming a drugreceptor complex), it pushes equilibrium to produce
more “inactive” receptors in the cell.
What really helped us with better understanding
the concept of inverse agonists is the graph we made
and have presented here. Whenever we find ourselves
getting confused about how an inverse agonist works,
or how it differs from a neutral antagonist/full agonist,
we visualize this graph in our heads. Seeing that an
inverse agonist actually produces a lower response
curve than an antagonist, and an opposite curve to the
full agonist, definitely helps in re-integrating what it
does to receptor response.
Most importantly, don’t get too stressed out if you don’t understand some of the content
immediately in class. You have great teachers, T.A.s and peers, especially your cell bio group, to
help you out during any times of need. Perhaps the hardest part of this class is actually being able to
look at material in a different light. This will aid you immensely in better understanding what is
presented. It is actually encouraged that you look at different alternatives to both theoretical and
application based content. Keeping this in mind will benefit you throughout the course !.
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