Download Introduction / The Flow of Information

Introduction
INSTRUCTOR
Professor Danton H. O'Day, Ph.D.
Department of Biology--Room 2003
University of Toronto at Mississauga
Email: [email protected]
Contact the course instructor if you require general help on lecture material. Make sure you have read the
online lecture material and any pertinent textbook chapters prior to seeking help from your instructor.
Introduction
The cell is the "unit of life". Its survival and function requires an ongoing, dynamic interaction between all of
its internal components. These internal functions must also work in concert with events occurring both at the
cell surface and in the extracellular environment. The goal of this course is to teach students about these
interactions so that they begin to understand to complexity of cellular structure and function. We will do this
by first dismantling the cell and discussing many of its constituents. After discussing how they function and
how they interact with other components, we will begin to show how the cell is more than the sum of its
parts.
Student Responsibilities
Every student must read the lectures prior to class and be prepared to discuss the content. The lectures will
focus on clarifying and extending the understanding of essential concepts. It will not involve a reiteration of
the online facts. Instead it will show the importance of the material and will involve the discussion of current
issues based on student interest.
Course Rules
• You must attend tutorials
• Lectures are optional but if you miss a lecture, it is your responsibility to catch up
• Talking is a No-No during class discussions
• If you have a question, raise your hand to ask a question
• If you have difficulties, don't wait until the day before the test to ask for help
• We won't be rescheduling tests or due dates for lab reports, so make up a schedule now
About Tutorials
The tutorials have been designed to complement the lecture material and to help you as you understand the
complexity of cell function. Your Teaching Assistant will discuss how he/she will run the tutorials during
your first tutorial session.
• Many changes this year
• No Laboratory exercises; Mandatory Tutorials
• Do not plagiarize material from the web or elsewhere; we will follow University guidelines in dealing with
this situation should it arise.
Teaching Assistants
For help with tutorial material contact your teaching assistant not Professor O'Day. Setting up an
appointment via email is the best way to guarantee a respectable amount of time for discussing lab related
material. When meeting with your TA be sure to bring all of your work. Don't expect answers to problems
when you haven't attempted to solve problems independently.
Textbook & Supplementary Reading
Karp, 2005. Cell & Molecular Biology: Concepts & Experiments with CD-ROM, Fourth Edition, John
Wiley & Sons, Toronto; ISBN 0-471-46580-1. Where necessary you must review the material covered in the
pre-requisite courses. I don't assign readings, if you don't understand a topic, or are interested in it, look it up
in the index of your textbook.
Animated Cell Biology
If you are having any trouble with understanding some of the concepts or want to learn more about other
areas not covered in lecture, check out the Animated Cell Biology website at:
http://www.utm.utoronto.ca/~w3cellan/. There are about 50 animations there with open access.
Lecture Overview
Note: Students are required to read the specific on-line lecture material before coming to lecture. In lecture
we will discuss the important concepts covered in the on-line material for that lecture and their implications.
In mandatory tutorials, we will cover some fundamentals to help you better understand the lecture content.
Part I. Cell Adhesion, Communication and Signal Transduction Basics
Sept 11
Introduction & The Flow of Information
Sept 13
The Cell Membrane
Sept 18
From Cells to Tissues: Cell Junctions
Sept 20
Cell Communication and Gap Junctions
Sept 25
Cell Adhesion Molecules: Types & Functions
Sept 27
Signal Transduction via Surface Receptors
Oct 2
Signal Transduction: cAMP Signaling from Receptor to Function
Oct 4
Lecture Test 1 (1h)
Oct 9
Thanksgiving: No class
We begin with cellular compartmentalization and how information flows inside the cell. This will lead to
the structure and function of the cell membrane with a focus upon how cells adhere to each other and how
they communicate. As transducers of extracellular events that lead to cellular responses, receptors in the
cell membrane will be analyzed, leading to a discussion of how an extracellular signal such as a hormone
can lead to a cellular response. This area of signal transduction will introduce the diversity of cellular
signaling while focusing on well characterized systems beginning with cyclic AMP-mediated signalling.
After Thanksgiving, a one hour term test will be given. I will discuss the organization of the test at the start
of October.
Part II. Signal Transduction, The Cytoskeleton & Cell Movement
Oct 11
The Dual Signalling Pathway: Inositol Phosphates and Protein Kinase C
Oct 16
The Dual Signalling Pathway: Calcium & Calmodulin
Oct 18
Cross-Talk, Signal Amplification & Cascade Mechanisms
Oct 23
Microtubules & Motor Proteins
Oct 25
Microfilaments, Myosins and Microbes
Oct 30
Chemotaxis & the Inflammatory Response
Nov 1
Biomembrane Fusion: Virus Induced Fusion
Nov 6
Lecture Test 2 (1h)
Cell signalling requires that pathways can intercommunicate to ensure proper functioning. After examining
this we will concentrate on a few intracellular systems that are regulated by signalling events. In addition if
the cellular events are to function properly they must be organized within the cell. Here we will examine the
cytoskeletal system of cells and how their involvement in cell shape and motility. The subject of
biomembrane fusion will also be discussed. All of these component structures and events will ultimately be
linked together to explain issues such as cancer cell metastasis. The second term test will cover all lectures
up to that point.
Part III. Protein & Vesicle Trafficking & Disease
Nov 3
Lysosomes in Normal Cells & the Disease Process
Nov 15
Protein Targeting
Nov 20
Receptor-Mediated Endocytosis: The Events
Nov 22
Receptor-Mediated Endocytosis: Cholesterol Uptake and Cholesterolemia
Nov 27
Vesicle Traffic: COPs, SNARES & Other Things
Nov 29
Cell Biology of Cancer
Dec 4
EGFR Signaling and Breast Cancer
Dec 6
Final Lecture Test
The lysosome is a simple structure with critical cellular roles. The way proteins and other components are
targeted to specific cellular locales such as lysosomes will be covered followed by an analysis of how the
cytoskeleton moves proteins and organelles within the cell. Receptor mediated endocytosis and intracellular
vesicular movements will complete the picture and bring us back to our first and subsequent lecture topics.
All of this information will all be integrated through the analysis of how normal and cancer cells move.
Grading Scheme & Important Dates (These dates will not be changed)
Oct 4
Lecture Test 1 (in lecture) 20%
Tutorial Test 1 (in tutorial
Oct 16
10%
section)
Nov 6
Lecture Test 2 (in lecture) 25%
Tutorial Test 2 (in tutorial
15%
Nov 21
section)
Contribution to Tutorials 5%
Final Lecture Test (in
25%
Dec 6
lecture)
Total
100%
Marks
Important Notes
The scheduled dates for tests and quizzes will not be changed except for valid reasons. If a scheduled test or
quiz conflicts with a cultural or religious holiday/event you must provide written documentation to Professor
O'Day as soon as the date of that event becomes public knowledge. If you are ill, you must provide a
Doctor's note as soon as you return to campus. Failure to do so could mean that your request for alternative
scheduling may not be allowed. Typically make-up tests and quizzes will consist of oral examinations at a
date/time mutually suitable to the student and professor.
The Flow of Information
Lecture Outline
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Introduction
Cellular Compartmentalization
Flow of Information Between the Nucleus & Cytoplasm
From Cell Membrane to Nucleus
Understanding Cells is Essential
Course Tid-Bits: Cholesterol: Good or Bad?
Conclusions
Introduction
No cellular process or structure is defined by a single molecule or constituent. There is no primary molecule
or single essential molecule. While the loss of a single molecule may be lethal, that molecule alone does not
comprise the living cell. Even the most mundane molecule serves an important role in the life of the cell. In
this course we will look at selected cellular components and describe their various cellular roles. More
importantly, we'll see how these components interact. Rather than simply listing cellular constituents and
their functions, a major goal of this course is to demonstrate the dynamic interplay between diverse cellular
constituents. After you understand what the primary functions of each component are, then you will be
shown how they interact with or are regulated by other cellular constituents. This is the new era of cell
biology that is emerging. We've past the "Modern Cell Biology" phase and are now moving into what might
be considered the "Dynamic Cell Biology" era-understanding how the functions of each component intersect
with all others and how they mediate the event we call "life". We may not reach this goal-since many
answers are a long way off-but along the way we should understand how interesting cells are and how
complex their lives can be. Let's begin with a general introduction starting with how different cellular jobs
are localized to certain cellular organelles, structures or regions. Most of this material is review from prerequisite courses.
Cellular Compartmentalization
Cellular processes are compartmentalized within the cell. Some cellular compartments are clearly evident as
distinct organelles that house specific components to carry out specific processes. Here's a general review
diagram of most of the major compartments in eukaryotic cells.
Other cellular compartments are less evident. For example, lipid rafts and caveolae in the cell membrane
serve to localize specific proteins and lipids. These will be discussed throughout the course.
Flow of Information Between the Nucleus & Cytoplasm
The survival of the cell depends upon its ability to respond to the world around it. Information flow within
the cell regulates how the cell acts or changes (e.g., during development cells specialize). The nuclear
genome is encoded in the chromosomal DNA. Genes are regulated and transcribed to make RNA which
flows into the cytoplasm to direct protein synthesis. Regulatory molecules that control which genes are
activated and deactivated flow into the nucleus. Subunits, enzymes and other components that are made in
the cytoplasm need to move into the nucleus for it to function. These events are shown in the next figure.
The following points need emphasis:
• Nuclear genome--DNA in Chromosomes/chromatin
• RNA synthesized & modified in nucleus
• Proteins made in cytoplasm (never in nucleus)
• Proteins often are post-translationally modified in cytoplasm
• Regulatory proteins "tell" which genes to be active
From Cell Membrane to Nucleus
As we will detail in our lectures on signal transduction, cells respond to external signals from other cells in
the body. These responses may involve short-term physiological changes. Or, they may result in the
activation of genes leading to long term changes. As shown in the diagram below, the activation of genes in
the nucleus begins with the binding of a ligand to a receptor in the plasma membrane (cell membrane). This
is followed by activation of downstream signaling components which typically are protein kinases (enzymes
that add phosphate groups to other proteins). These in turn activate transcription factors which move into the
nucleus to regulate gene activity. There are many signaling routes to gene regulation.
Understanding Cells is Essential
As the unit of life, the cell not only underlies normal biology, it is also the target for disease. While the study
of cells is a goal in itself, the understanding that is gained will help in finding cures for many diseases. In this
course, we'll look at several aspects of many different diseases. Here are a few examples and the topics we'll
cover:
• Cancer--cell surface, cell-cell communication
• AIDS--Membrane fusion, signal transduction, receptors
• Tay Sachs/Arthritis--Lysosomes; gene replacement therapy
Course Tid-Bits
Throughout the course, we'll give some information of general interest about various topics. For example,
there is an on-going debate about cholesterol. The assumption is that cholesterol is bad for you. Is this true?
Here are some interesting facts about cholesterol, with more to come later.
• Cholesterol is a critical steroid molecule
• Cholesterol stabilizes the cell membrane
• Cholesterol links critical proteins to the membrane
• Cholesterol synthesis inhibitors induce abnormalities in forebrain development (holoprosencephaly; arrow
figure below; Porter et al, 1996. Science 274: 261.)
©Copyright 1998-2006 Danton H. O'Day