FSN 1500 Week 8

1. FSN 1500 Week 8 Cell Division and Related Topics

2. Cell Division • Cell division is necessary for the growth, repair and reproduction of any organism • Next week you’ll learn that the uncontrolled replication (division) of damaged cells constitutes cancer • The knowledge produced by studying cellular division processes is the basis for gene therapy, genetic testing and engineering, stem cell manipulation and cloning; application of some of this research, as stated previously, is highly controversia1!

3. Cell Division Terminology • Chromosomes - coiled filament structures composed of DNA (deoxyribonucleic acid), RNA (ribonucleic acid) and proteins; carriers of the genetic code; each undamaged human cell (other than sex cells and a few other exceptions like red blood cells) contains 46 chromosomes (23 pairs)

4. Cell Division Terminology • Each chromosome pair prior to cell division consists of two genetically identical parts (chromatids) connected at the centromere (see figure)

5. Chromosomes • Complexity of organism not directly related to cell chromosome number • Chromosomes can be viewed by preparation of a karyotype (figure): chromosomes are photographed, enlarged, and the enlarged segments paired by size

7. Chromosomes • In human cells the first 22 equal length chromosome pairs are called autosomes; the twenty-third pair (unequal length in males) is called the sex chromosome (determines sex of offspring) (see figure) • Males carry XY sex chromosome pair, females XX; Who determines the sex of the offspring?

8. Genes • Gene - section of a chromosome that contains the genetic information for the creation of a specific protein; some of these proteins can control the development of an inherited trait (e.g., skin color, eye color, attached/unattached ear lobes, etc.) • Telephone cord analogy • Some researchers have also suggested that genes may also control or strongly influence our predispositions to future weight, height, personality, etc. • Nature versus nurture??

9. Cell Division • The life cycle of animals requires two types of cell division: mitosis and meiosis • Mitosis - required for growth and repair; cell division in which the daughter cells (replicates) contain the same number and types of chromosomes as the parent cell • Meiosis - required for reproduction; cell division that occurs during production of sex cells (gametes: male - sperm in testes; female - egg in ovaries)

10. Cell Division • In Meiosis original genetic material of organism is halved (the human sperm and egg cells each contain 23 chromosomes) • The complete compliment of chromosomes in an animal cell known as the diploid number (2N); one half this number referred to as the haploid number (N) of chromosomes

11. Animal Life Cycle • In the life cycle of animals, sperm with the haploid chromosome number fertilizes an egg with the haploid number of chromosomes resulting in the production of a zygote (fertilized egg with the diploid number of chromosomes) (see figure) • The zygoteundergoes mitosis and cell specialization; mitosis continues in any offspring produced until death

12. Animal Life Cycle Changes 2013 8/9/2010

13. Cell Cycle • Duplication of non-sex cells, the cell cycle (see figure), consists of mitosis and interphase • Interphase is the longest component of the cell cycle, in typical animal cells (e.g., your outer skin) it lasts 18-24 hours; cell specialization, maturation and DNA synthesis occurs during interphase

14. Applies to non-sex cell division

15. Cell Division (Mitosis) • Before mitosis can begin the DNA of the cell to be duplicated must be reproduced: chromatin condenses to chromosomes containing sister chromatids attached at the centromere • Mitosis has four identified stages: prophase, metaphase, anaphase, telophase - in the typical animal cell mitosis takes about one to two hours • The average adult sheds 50,000 skin cells every minute!!

16. Mitosis Overview

17. Cell Division (Mitosis) • Mitosis Overview (prior see figure): • Prophase: nuclear envelope starts to disappear; centrioles, attached by spindle fibers, move toward top and bottom of cell • Metaphase: nuclear envelope gone; cell starts to elongate; asters created, chromosomes migrate to equator of cell along spindle fibers

18. Cell Division (Mitosis) • Anaphase: cell further elongates; spindle fibers separate; individual sister chromatids migrate along spindle fibers to opposite ends of elongated cell; asters disappear • Telophase: most of spindles disappear; nuclear envelope and nucleolus reform encapsulating chromatids, cell furrows until it breaks into identical pair; chromatin reforms in each cell

20. Cell Division (Mitosis) • There’s a good online simulation of mitosis available via the Cells Alive home page (http://www.cellsalive.com/)

21. Cell Division (Mitosis) • Most animal cells divide about 50 – 75 times before degenerative processes lead to cell death (apoptosis); exception - cancer cells retain the ability to divide repeatedly! • Why???

22. Cell Division • One hypothesis: normally the ends of chromosomes (telomeres) gradually unravel and shorten during mitosis until the cell can’t successfully complete the process, leading to apoptosis • However, cancer cell telomeres don’t unravel, apparently due to secreting an abundant amount of the enzyme that inhibits the telomere shortening Pink color - telomeres

23. Cell Division • Cell aging can be postponed by reduced temperatures - basis for cryogenics (see slide)

24. Cell Cryogenics • The common wood frog (top) essentially freezes solid during the winter and exhibits no movement, breathing, heartbeat or brain activity! • Scientists studying the frog’s freeze/thaw mechanism hope to someday successfully freeze and thaw human transplant organs, thus increasing the number of successful transplants which could be performed

25. Cell Cryogenics • Some success has been achieved in cryopreservation of animal organs (e.g., rabbit) for later transplant, but not yet for humans

26. Cell Division (Meiosis) • Meiosis involves similar, but more complicated steps, resulting in the production of sex cells with the haploid (N) number of chromosomes (see figure)

27. Genes and Heredity • Scientists previously estimated that each human cell’s 46 chromosomes contained 100,000 to 200,000 genes! • However, since 2013, the estimate is now as few as 19,000 genes – as many as 200 acquired from bacteria!

28. Genes and Heredity • Genes are segments of chromosomes; genes are composed of different length strands of DNA (long, thread-like intertwined molecule, called the double helix); the critical components are four substances called nucleotide bases: adenine (A), cytosine (C), thymine (T), guanine (G)

29. Genes and Heredity • The four bases pair in the possible arrangements A with T, and C with G to form the rungs of the DNA ladder; these base pairings transcribe (record) the genetic code (see figure) • There are about 3 billion base pairs on the 46 chromosomes in each human cell! mistake

30. Genes and Heredity • The information equivalent of the 3 billion base pairs (if all are meaningful) may be about 1000 books of 1000 pages each (one million pages)! • Apparently many of the cell’s genes are inactive during certain times of our lives and activated when needed by “control switches” (segments of DNA sometimes called control genes) • The latest studies also suggest that significant sections (maybe close to 98%) of the genome contain base sequences that don’t code for the creation of any protein (previously called junk DNA)!; these DNA sequences may be the “control switches” • What “throws the switches”?

31. Emerging Science Source: Nutrition Action Health Letter, July/August 2013

32. Genes and Heredity • We carry two copies of each gene, each parent supplies one • Sometimes a genetic disease doesn’t develop if one of the genes isn’t flawed • Studies suggest that even a single base pair error in a gene’s DNA code (perhaps 30,000 or more base pairs long) could result in disease

33. Genes and Heredity • Human Genome Project - scheduled 15 year (began in 1990, now partially complete), $3 billion international project whose goal is to identify the position of all genes on the 46 chromosomes and discern their makeup (base pair order) and function • Currently the position and function of about 2500 genes identified • There are about 4000 genetic-related diseases!

34. Genes and Heredity • During Summer 2000, Celera Genomics (private company) and the U.S. National Institutes of Health announced that the entire genome had been sequenced (all the base pairs identified) - however, the identification of all the genes and their functions will take much longer

35. Genetic Research Implications • If we develop a complete genetic map of humans what are the benefits and disadvantages? • BENEFITS: • Genetic testing can discern who (even a fetus) is predisposed to certain diseases so possible avoidance behaviors/medications can be used

36. Genes and Heredity • Genetic screening (e.g., companies like 23andMe) is now available to detect, or predict the likelihood of a person contracting more than 1300 diseases! (Full genome sequencing still too expensive for the individual.)

37. Genes and Heredity • The future? Advances in genetic testing may soon allow an entire genome to be inexpensively sequenced. • Last year the FDA asked 23andMe to cease its commercial operations

38. Genes and Heredity • Gene Therapy - the ultimate in microsurgery; attempts to repair or replace damaged genes - see figures

39. 1990

41. Gene Therapy History • In 1999, an 18-year-old male died from massive organ failure three days after receiving a gene therapy treatment • In October 2002 the U.S. government suspended all gene therapy trials in the U.S. after a second person undergoing gene therapy developed a rare form of leukemia • In March 2005 a U.S. Food and Drug Administration panel suggested that the gene therapy trials resume on a limited basis

42. Gene Therapy Update • Until 2007, gene therapy only worked consistently well at treating the Severe Combined Immunodeficiency Disease (SCID) we discussed earlier (the two young girls) • In 2008, researchers at the University of Pennsylvania medical school achieved some success in using gene therapy to treat a form of blindness • Also in 2008, a researcher at the Baylor College of Medicine in Texas has used a gene therapy to cure a rare form of blood cancer

43. Gene Therapy Update • Scientists are apparently finding ways to minimize the negative effects associated with using viruses to carry the “medicinal” genes to the target cells, while others are starting to use biodegradable nanoparticles as carriers of the treatment genes • As of 2014, most researchers are again very excited about the prospects of gene therapy to eventually cure numerous diseases

44. Genetic Research Implications • DISADVANTAGES: • Who controls the knowledge and has access to its applications? • Since we all are estimated to have 50-60 damaged genes, will genetic discrimination occur? (see figure)

45. Genetic Research Implications?

46. Genetic Research Results • Will couples try to design the perfect child or groups a perfect race (designer genes)?

47. Genetic Research Results • Will our lifespans be extended beyond current comprehension, necessitating a total revision of social systems? • Review the following figures of newspaper articles. Stay alert to this fast-paced topic.

49. Genetic Research Implications • March, 2002: the media published reports of the widening availability of Preimplantation Genetic Diagnosis (PIGD). • In this technique, eggs are harvested from a female and fertilized in vitro (e.g., laboratory) – the zygotes divide outside the womb into eight-cell embryos • The eight-cell embryos are then tested for genetic disease(s); one free of the damaged gene(s) is implanted into the mother; the other embryos are either frozen, destroyed or donated to research.

50. Genetic Research Implications • Related issue: animal and human cloning (production of an organism with the exact genetic blueprint of the original); Dolly the sheep was the first (1996) successful cloning of a larger mammal. • The cloned animals, to date, have been produced by a technique called somatic cell nuclear transfer (SCNT)