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Ch 12: Cell Cycle 2016 Chapter 12: Cell Cycle From Topic 1.1 (in PowerPoint lecture) Understandings: • Specialized tissues can develop by cell differentiation in multicellular organisms. • Differentiation involves the expression of some genes and not others in a cell’s genome. • The capacity of stem cells to divide and differentiate along different pathways is necessary in embryonic development and also makes stem cells suitable for therapeutic uses. Applications and skills: • Application: Use of stem cells to treat Stargardt’s disease and one other named condition. • Application: Ethics of the therapeutic use of stem cells from specially created embryos, from the umbilical cord blood of a new-born baby and from an adult’s own tissues. International-mindedness: • Stem cell research has depended on the work of teams of scientists in many countries who share results thereby speeding up the rate of progress. However, national governments are influenced by local, cultural and religious traditions that impact on the work of scientists and the use of stem cells in therapy. Utilization: • The use of stem cells in the treatment of disease is mostly at the experimental stage, with the exception of bone marrow stem cells. Scientists, however, anticipate the use of stem cell therapies as a standard method of treating a whole range of diseases in the near future, including heart disease and diabetes. Aim 8: There are ethical issues involved in stem cell research, whether humans or other animals are used. Use of embryonic stem cells involves the death of early-stage embryos, but if therapeutic cloning is successfully developed the suffering of patients with a wide variety of conditions could be reduced. From Topic 1.6 Essential idea: Cell division is essential but must be controlled. Nature of science: Serendipity and scientific discoveries—the discovery of cyclins was accidental (1.4). Understandings: • Mitosis is division of the nucleus into two genetically identical daughter nuclei. • Chromosomes condense by supercoiling during mitosis. • Cytokinesis occurs after mitosis and is different in plant and animal cells. • Interphase is a very active phase of the cell cycle with many processes occurring in the nucleus and cytoplasm. • Cyclins are involved in the control of the cell cycle. • Mutagens, oncogenes and metastasis are involved in the development of primary and secondary tumours. Applications and skills: • Application: The correlation between smoking and incidence of cancers. • Skill: Identification of phases of mitosis in cells viewed with a microscope or in a micrograph. • Skill: Determination of a mitotic index from a micrograph. Guidance: • The sequence of events in the four phases of mitosis should be known. • Preparation of temporary mounts of root squashes is recommended but phases in mitosis can also be viewed using permanent slides. • To avoid confusion in terminology, teachers are encouraged to refer to the two parts of a chromosome as sister chromatids, while they are attached to each other by a centromere in the early stages of mitosis. From anaphase onwards, when sister chromatids have separated to form individual structures, they should be referred to as chromosomes. Chapter 12: Cell Cycle From Topic 1.6 International-mindedness: • Biologists in laboratories throughout the world are researching into the causes and treatment of cancer. Utilization: • The mitotic index is an important prognostic tool for predicting the response of cancer cells to chemotherapy. Aim 8: The tobacco industry could be discussed. Suppression of the results of research by tobacco companies into the health effects of smoking tobacco was unethical. Smoking causes considerable social harm, but, with the exception of laws on production and supply in Bhutan, has never been made illegal. From Topic 3.1 Understandings: • The genome is the whole of the genetic information of an organism. From Topic 3.4 Understandings: • Radiation and mutagenic chemicals increase the mutation rate and can cause genetic diseases and cancer. Applications and skills: • Application: Consequences of radiation after nuclear bombing of Hiroshima and accident at Chernobyl. From Topic 6.4 Applications and skills: • Application: Causes and consequences of lung cancer. Aim 8: The social consequences of lung cancer and emphysema could be discussed. Key Roles of Cell Division • Reproduction, Growth &Development, and Repair • Reproduction - Unicellular divide from one to two to reproduce entire organism (fission, budding) - Multicellular organisms grow and develop or replace damaged or dead cells. • Cell division results in identical hereditary material and two daughter cells. Cellular Division • Replicates the DNA exactly. • Allocates two copies of DNA to opposite ends of the cell. • Separates into two daughter cells. Heredity • Total hereditary material of a species is called its genome. • Offspring acquire genes from parents by inheriting chromosomes. • DNA- Nucleic acid that codes for the formation of proteins. Made of four different nucleotides. • Genes- The length of DNA that codes for a protein. • Chromosomes- Sections of DNA that contain genes and other associated DNA; makes it possible for large eukaryotic genomes to go cellular division. Chromosome Condensation http://www.dnalc.org/view/15482-DNA-packaging-3D-animation-with-advancednarration-and-labels.html • • DNA coils around 8 Histone Proteins and then keeps coiling to condense to be a chromosome Nucleosomes are the “beads” made of DNA coiled around Histones. Parts of A Chromosome Parts of A Chromosome Kinetochores Cell Cycle Overview http://www.wiley.com/college/test/04717871 59/biology_basics/animations/mitosis.swf Phases of the Cell Cycle • Interphase: when cell grows, copies its chromosomes, and prepare for cell division • 90% of cell cycle • lots of activity • Metabolism, Protein synthesis, DNA Replication and increase in number of mitochondria and chloroplasts. • Three phases • • • G1: First growth phase (G = gap) S: Synthesis G2: Second growth phase Cell Division: Mitotic (M) Phase • M Phase contain two parts: • Mitosis: division of nucleus • Cytokinesis: division of the cytoplasm http://www.sumanasinc.com/webcontent/ani mations/content/mitosis.html Mitosis • Very reliable (one error in 100,000 divisions) • Mitosis: has four stages (PMAT) • Prophase • Metaphase • Anaphase • Telophase Mitosis: Prophase • Prophase • Nucleoli disappear • Chromatin condense • Spindle forms and attaches to Chromosomes • Centrosomes move apart Mitosis: Metaphase • • • • • Metaphase The centrosomes are at opposite ends Chromosomes are at metaphase plate Centromeres are all lined up Spindle fully formed. • How was this possible? http://bcs.whfreeman.com/lodish5e/content/cat_010/2001001.htm?v=chapter&i=20010.01&s=2000 Mitosis: Anaphase • Sister chromatids split • Kinetochore fibers shorten • Nonkinetochore fibers lengthen and motor proteins “walk” past How Sister Chromatids Gets Separated? • Microtubules shorten on their kinetochore ends instead of their spindle pole ends. Mitosis: Telophase • Nonkinetochore further elongate • Daughter nuclei begin to form • By the end, the two nuclei are clearly visible in their interphase appearance. Animal Telophase Plant Telophase Cytokinesis • In animal cells, pinching forms a cleavage furrow. • Contractile ring of actin fibers pinch the cells in two. • In plant cells, the golgi apparatus secretes vesicles that fuse in the middle to form the cell plate. More will be added until a new middle lamella forms and new cellulose is laid down on either side. http://highered.mheducation.com/sites/9834092339/student_view0/chapter10/animation_-_cytokinesis.html Cell Cycle Control System • Check points or switches control the rate of the cell cycle • Can either be intracellular and extracellular control • G1 checkpoint or the Restriction point is said to be the beginning of the cell cycle. • G0 state is the resting state Cell Cycle Regulation: Intracellular • Protein kinases are enzymes that transfer a phosphate group from ATP to a target protein • They can either activate or inactivate • Some kinases give the “go-ahead” signal to bypass the G1 and G2 checkpoints. • They are present at constant concentration, but are usually in inactive “dormant” form. • These kinases are regulated by cyclins, a protein that cyclically fluctuates in concentration inside the cell. • Kinases that need cyclins to be active are called cyclin-dependent kinases called Cdks. Cdk: MPF • MPF: a type of Cdk that was first discovered in the cell; short for “maturation-promoting factor” or “M-phase-promoting factor” since it triggers the cell to pass G2 checkpoint into M phase • Acts directly as a kinase as well as activating other kinases Cdk: MPF Review • • • • http://www.sinauer.com/cooper5e/animation1604.html http://highered.mcgrawhill.com/olcweb/cgi/pluginpop.cgi?it=swf::535::535::/sites/dl/free/007 2437316/120082/bio34a.swf::Control%20of%20the%20Cell%20Cycle http://www.cleanvideosearch.com/media/action/yt/watch?v=QGx50C 1w8YY http://www.nobelprize.org/educational/medicine/2001/cellcycle.html Cell Cycle Regulation: External Factors • Chemical Factors • All kinetochores need to be attached to chromosomes in order for anaphase to begin. • Growth factors • Physical factors • Density Dependent Inhibition: when cells get crowded, they stop dividing. • Anchorage dependence: cells must be attached to substratum (an underlying layer of substance) Differentiation • Differentiation: or “differential gene expression” (from Ch 19.2 of your Campbell textbook); expression of different genes by cells with the same genome • Stem Cells: an undifferentiated cell that is capable of giving rise to indefinitely more cells of the same type, and from which certain other kinds of cell arise by differentiation http://www.sumanasinc.com/webcontent/animations/content/stemcells_scnt.html Stem Cell Research • The Promise of Stem Cell Research: Ted Talk https://www.ted.com/talks/susan_solomon_the_promise_of_research_with_stem_cells • Stem Cell Stories: • Stargardt’s Disease: • Stargardt’s Disease and Stem Cell Research: http://www.eurostemcell.org/films#ipsfilm http://www.youtube.com/watch?v=vvrlpVPxYiE http://www.blindness.org/index.php?view=article&id=2636%3Aclinical-trial-recruitment-underway-for-stem-celltreatments&option=com_content&Itemid=120 Intro to Cancer • Tumor is a mass of cells that have lost their ability to stop dividing. • Malignant Tumors: • Can impair normal function of tissue, organ • Altered cell cycle, excessive divisions • May have different # of chromosomes • Altered metabolism • Doesn’t not show DDI • Benign Tumors: • • Stay at the original site Don’t impair normal function usually Cancer Cells • • • • No response to DDI May make excess growth factors May have different signaling systems Normal checkpoints are not working • Are considered transformed cells (neoplastic transformation) Metastasis • Metastasis- cells move from original location • move in blood, lymph vessels • can be treated with radiation, chemotherapy. Lung Cancer Causes: • Smoking • Passive Smoking • Asbestos Fibers • Radon Gas • Family history • Lung Disease • Air pollution (1-2% of lung cancer deaths attributed to this) Consequences: • Chronic, hacking, raspy coughing, sometimes with blood-streaked mucus • Recurring respiratory infections, including bronchitis or pneumonia • Increasing shortness of breath, wheezing, persistent chest pain • Hoarseness • Swelling of the neck and face • Pain and weakness in the shoulder, arm, or hand • Fatigue, weakness, weight loss, and appetite, intermittent fever, sever headaches, and body pain • Difficulty swallowing Radiation Risks Summary of Radiation Injury Clinical Symptoms and Findings: Hiroshima and Nagasaki, from Manhattan Engineer District Day after Explosion 1. Most Severe 1. Nausea and vomiting Moderately Severe 1. Nausea and vomiting 2. 3. after 1-2 hours. NO DEFINITE SYMPTOMS after 1-2 hours. 4. 5. 6. 2. Diarrhea 3. Vomiting 7. 4. Inflammation of the mouth and throat 8. 9. 5. Fever 6. Rapid emaciation 10. Death 11. (Mortality probably100%) Mild NO DEFINITE SYMPTOMS NO DEFINITE SYMPTOMS 2. Beginning epilation. 12. 13. 14. 15. 16. 17. 18. 19. 3. Loss of appetite and general malaise. 1. Epilation 20. 21. 4. Fever. 5. Severe inflammation 2. Loss of appetite and malaise. 22. of the mouth and throat 3. Sore throat. 23. 24. 25. 26. 4. Pallor. 5. Petechiae 6. Diarrhea 7. Moderate emaciation. 27. 28. 6. Pallor. 7. Petechiae, diarrhea 29. and nose bleeds 30. 31. (Recovery unless complicated by previous 8. Rapid emaciation poor health or Death super-imposed in- (Mortality probably 50%) juries or infections).