ADVANCED CELL BIOLOGY - BIO315F
Professor Danton H. O'Day
INSTRUCTOR
Professor Danton H. O'Day, Ph.D.
Department of Zoology--Room 2003
University of Toronto at Mississauga
Email: bio315h@utm.utoronto.ca
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, 2008. Cell & Molecular Biology: Concepts & Experiments with CD-ROM, 5th, John Wiley & Sons, Toronto. 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.n lecture I will not review all of the details covered in that online material but instead will focus on the important concepts and their relevance. In mandatory tutorials, we will cover some fundamentals to help you better understand the lecture content.
Part I. Cell Adhesion, Communication and Signal Transduction
Sept. 8 Introduction & The Flow of Information
Sept. 10 The Cell Membrane
Sept. 15 From Cells to Tissues: Cell Junctions
Sept. 17 Cell Communication and Gap Junctions
Sept. 22 Cell Adhesion Molecules: Types & Functions
Sept. 24 Signal Transduction via Surface Receptors
Sept. 29 Signal Transduction: cAMP Signaling from Receptor to Function
Oct. 1 The Dual Signalling Pathway: Inositol Phosphates and Protein Kinase C
Oct. 6 The Dual Signalling Pathway: Calcium & Calmodulin
Oct. 8 Cross-Talk, Signal Amplification & Cascade Mechanisms
Oct. 13 Thanksgiving: No Class
Oct. 15 Midterm Test (50min; in lecture)
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. 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. 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. The Cytoskeleton, Intracellular Trafficking & Disease
Oct .20 Microtubules & Motor Proteins
Oct .22 Microfilaments, Myosins and Microbes
Oct. 27 Chemotaxis & the Inflammatory Response
Oct. 29 Biomembrane Fusion: Virus Induced Fusion
Nov. 3 Lysosomes in Normal Cells & the Disease Process
Nov. 5 Protein Targeting
Nov. 10 Receptor-Mediated Endocytosis: The Events
Nov. 12 Receptor-Mediated Endocytosis: Cholesterol Uptake and Cholesterolemia
Nov. 17 Vesicle Traffic: COPs, SNARES & Other Things
Nov. 19 Nucleocytoplasmic Transfer
Nov. 24 Nuclear and Nucleolar Localization Sequences
Nov. 26 Cell Biology of Cancer
Dec. 1 Epidermal Growth Factor (EGFR) Signaling Pathways
Dec. 3 EGFR Signaling and Breast Cancer
Exam Period - Final Lecture Exam (3h)
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 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. 6 Tutorial Test 1 (in tutorial section) 10%
Oct. 15 Lecture Test 1 (in lecture) 20%
Dec. 1 Tutorial Test 2 (in tutorial section) 15%
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Contribution to Tutorials 5%
Examination Period Final Lecture Exam 50%
Total Marks 100%
Important Notes

1. Test Dates. 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 as soon as the date of that event becomes public knowledge. If you are ill, you must provide an original copy of your completed UofT medical certificate as soon as you return to campus.

2. Make-up Tests. There will be no make-up tests. If the mid-term lecture test is missed, then the value of that test will be added to the total value of the final exam. If tutorial test 1 is missed, the value of that test will be added to tutorial test 2 or to the final grade depending on the situation. If tutorial test 2 is missed, then the value of that test will be added to the final exam total.


The Flow of Information
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 pre-requisite 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.)

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