week 2 summary

• C. elegans


  A round worm

  
  

  Used particularly for nervous system development - only has 320 neurons

  
  

  Also fate mapping the WHOLE of development as very single cell could be tracked
• Why are C. elegans a good model?

  Small and transparent

  Easy to cultivate, grow on agar plates with bacteria for food

  Have a short life cycle (egg to adult is 3 days)

  40% of genes implicated in human disease have orthologues in worms, very similar
• Drosophila as a model organism discoveries

  Good for genetics

  
  

  Found that genes are located on chromosmes, chromosomal inheritance specifies gender, how genetic material exchange exposure to X-rays can cause mutations

  
  

  Important for body patterning, stem cell biology and reproductive biology advancement
• Advantages of Drosophila


  - Simple genome, only four chromosomes

  - Very inexpensive

  - Quick breeding, generation times are very short
• Disadvantages of Drosophila


  - invertebrates

  - lack blood vessels

  - don't generate antibodies to fight disease (so not useful for immunology)
• Zebrafish advantages


  - Vertebrates

  - 70% of human genes have a zebrafish counterpart

  - 84% of known disease-causing genes have a orthologue in zebrafish

  - the female fish spawn eggs that are externally fertillised, so embryonic development occurs externally and is easily accessed visually

  - rapid embryonic development

  - can induce mutations by adding substances to the water
• Zebrafish research advances


  Research focuses on neuronal development, body patterning (the role of specific genes during embryogenesis), cardiac development, muscle development, sleep, regeneration and cancer
• X laevis


  African clawed frog

  
  

  Lives in fresh water
• X. laevis advantages


  Most essential cellular and molecular mechanisms are highly conserved
• Frog early research


  Urine of pregnant women were injected into female frogs, and frogs laid eggs due to presence of hormones

  
  

  It was the fastest and most reliable pregnancy test in the 1960s.
• X laevis reseach advances

  Ovarian biology

  Neurobiology (vertebrate, siplar brain circuitry)

  Eye and vision research

  Heart development

  Immunology

  Cancer
• Chick research advantages


  Incubation period of only 21 days

  
  

  Human and chicks have highly similar stages of development, the fundamentals of early embryogenesis is learned from the chick
• G gallus


  Chick
• Chick research focus


  Early embryonic development

  
  

  Body patterning

  
  

  Reproductive biology
• Mouse research advantages


  They are mammals

  
  

  Very similar to physiological systems of humans

  
  

  They develop a range of similar diseases that affect these systems, and certain diseases not normally experimented by mice can be experimentally induced
• Mouse research disadvantage


  - Early acting mutant phenotypes difficult to study

  - Embryonic manipulations are difficult

  - Development and life cycle relatively slow (months)

  - Relatively expensive to maintain

  - Responses to therapeutics not always consistent with human

  - Physiology of a SMALL animal

  - Strict ethics
• Why are sheep used as models sometimes?

  For size similarity - used for things like foetal physiology, foetal respiratory, kidney development
• Advantages of humans as model

  Many diseases, 5000 genetically based

  Self-reporting mutants

  Some good family pedigrees

  Genome sequence complete
• Disadvantages of humans as models

  No experimental access

  Foetal material difficult to obtain

  Ethics

  Long generation time
• Are cells permanent?


  Cells may be permanent, or they can be renewable. In renewable tissues, cells that die or are exported must be replaced.

  
  

  E.g. skin is replaced every four weeks, hair constantly grows, nerve cells and heart tissue are not replacable
• How are blood cells formed?

  Through repeated cell divisions

  
  

  Cell specialisation generates the many cell types, but many will die
• Germ cell production


  Formation byy spermatozoa is through repeated cell divisions, meiosis and morphogenic changes

  
  

  There is a very high rate of cell date during spermatogensis - so that the best sperm cells possible are selected
• What type of tissue does not regenerate well?

  Cardiac muscle and nerves
• Goal of the cell cycle

  Produce two genetically identical cells from one precursor cell
• Cell cycle sequence


  G1 S G2 M

  
  

  Several checkpoints exist that determine whether cells continue through the cycle or enter apoptosis
• G0


  When cells (e.g. nerves) never leave G1 stage, it is called G0
• Gap 1 (G1) Phase


  First part of interphase, the longest

  
  

  Cell functions normally

  
  

  Protein and organelle synthesis occurs such that the cell doubles in size
• Cyclins and cyclin-dependent kinases

  Two key classes of regulatory molecules

  
  

  They determine a cell's progress through the cell cycle
• G1/S phase control


  Cyclin D binds to CDK4, resulting in the transcription of genes including cyclin E

  
  

  Cyclin E prepares the cell for S phase

  
  

  The levels of TFs that promote the expression of the S-phase cyclins and DNA synthesis enzymes increase

  
  

  Levels of the molecules involved in inhibition of entry into S phase are decreased
• Synthesis (S) phase


  DNA is replicated

  
  

  Replication begins at many sites along the length of the chromosome

  
  

  It is checked for any incorrect copying
• S phase control


  Active S cyclin-CDK complexes phosphorylate proteins that make up the pre-replication complexes on DNA replication origins

  
  

  This is to ensure that each pre-replication complex is activated to initiate chromosomal replication and new complexes are prevented from forming
• Gap 2 (G2) phase


  Cell prepares for mitosis

  
  

  Synthesis of components that ensure the survival and functionality of each daughter cell
• Mitosis (M) phase


  Myotin cyclin-CDK complexes are activated

  
  

  They promote stimulation of proteins involved in chromatin condensation, mitotic spindle formation, degrade chromsomal structure proteins and procession through the stages of mitosis
• Mitosis phases


  IPMAT
• Prophase - early


  Chromatin condenses to form chromosomes
• Prophase late


  Nuclear envelope disappears, spinle appartus forms
• Metaphase


  Spindles attach to centromeres, chromosomes line up along the mid point between poles
• Anaphase


  Centromeres divide, creating two chromosomes

  
  

  They are drawn to opposite poles of the cell

  
  

  Cell elongates
• Telophase


  Nuclear envelope reforms, furrow appears around the cell that will eventually pinch the cell into two new cells
• Two important proteins for cycle checkpoints

  Rb and p53