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Monday February 13th, 2017 Class 24 Learning Goals Differentiation and Organogenesis (case study: Drosophila) • After this class, you should be able to: • Identify cases of cellular differentiation and explain the evidence that supports this conclusion • Develop a narrative to explain the molecular mechanisms of differentiation in a particular cell or small group of cells • Evaluate the likelihood of molecular and cellular events in different parts of organogenesis Peer Instruction All fates possible No structures built Differentiation Role determined Mitosis, signaling, construction, etc 1 fate possible Specific structures 1) Where are the cells that are most differentiated? 2) Which cells have the most possible fates? 3) Do these cells have the same DNA? 4) How are differentiated cells different? Peer Instruction A zygote Stage 1 Does this cell have all possible DNA? Are all possible genes being expressed? Is this cell playing a final functional role or fate? An adult Does this cell have all possible DNA? Are all possible genes being expressed? Is this cell playing a final functional role or fate? Analyze this 8-cell organism. How are different cell fates determined? Peer Instruction gib2 Stage 1 Stage 9 Peer Instruction Arrows indicate directional mitosis. Letters are example genes turned on in this cell. gib2 gib2 Stage 1 gib2 gib2 gib2 gib2 gib2 tgg3 tgg3 Stage 2 Stage 3 zzk1 plub8 tgg3 tgg3 ipl6 ipl6 gib2 ipl6 ipl6 gib2 hr9 Stage 4 ipl6 thh4 thh4 hr9 ipl6 gib2 gib2 Stage 5 zzk1 Stage 6 s2cc zzk1 zzk1 plub8 thh4 thh4 thh4 hr9 hr9 hr9 Stage 7 thh4 hr9 Stage 8 Stage 9 Peer Instruction Between which stages is mitosis occurring? gib2 gib2 Stage 1 gib2 gib2 gib2 gib2 gib2 tgg3 tgg3 Stage 2 Stage 3 zzk1 plub8 tgg3 tgg3 ipl6 ipl6 gib2 ipl6 ipl6 gib2 hr9 Stage 4 ipl6 thh4 thh4 hr9 ipl6 gib2 gib2 Stage 5 zzk1 Stage 6 s2cc zzk1 zzk1 plub8 thh4 thh4 thh4 hr9 hr9 hr9 Stage 7 thh4 hr9 Stage 8 Stage 9 Peer Instruction The cells in stage 3 are all the same size and shape. How are they different? gib2 gib2 Stage 1 gib2 gib2 gib2 gib2 gib2 tgg3 tgg3 Stage 2 Stage 3 zzk1 plub8 tgg3 tgg3 ipl6 ipl6 gib2 ipl6 ipl6 gib2 hr9 Stage 4 ipl6 thh4 thh4 hr9 ipl6 gib2 gib2 Stage 5 zzk1 Stage 6 s2cc zzk1 zzk1 plub8 thh4 thh4 thh4 hr9 hr9 hr9 Stage 7 thh4 hr9 Stage 8 Stage 9 Peer Instruction There are many Hox genes that act as transcription factors for particular organs. FRUIT FLY Is it unusual to see great similarity in protein sequence between similar Hox genes in different species? Is it surprising to see Hox genes lined up in spatial order on a single chromosome? Head Thorax Abdomen MOUSE Peer Instruction Explain how gene expression changes the results of organogenesis in this region of the chicken embryo. Forelimb Chick embryo Forelimb In the areas where Hoxc6 and Hoxc8 are expressed together, ribs form Hoxc8 Hoxc6 Tuesday February 14th, 2017 Class 25 Learning Goals Cellular Signaling • After this class, you should be able to: • Propose an appropriate method of cell signaling for use by a given organism and situation • Describe the protein-protein interactions needed within a signaling system and predict the effects of stronger or weaker binding based on system details • Predict the source of and reason for a maternal determinant Peer Instruction 1) Explain how lipid soluble signals work. Steroid hormone Plasma membrane 2) Why is this ‘the easy way’? 2) What is a downside of using a signal that can enter any cell? Receptor in cytosol Nuclear membrane Nucleus Target gene DNA Peer Instruction Intercellular signal 1) How do membrane signal receptors work? Outside of cell Receptor protein in membrane Inside of cell 2) What is signal amplification? Second messengers Intracellular signals Peer Peer Instruction Instruction 1) Does a single cell have just one type of receptor? 2) What do all signal pathways share in common? Peer Instruction What is a ‘ligand?’ Peer Instruction What other signal-sending mechanisms do plants have? Smooth endoplasmic reticulum Tubule of ER passing through “plasmodesmata” Gap junctions Membrane proteins from adjacent cells line up to form a channel Peer Instruction Why is it advantageous for sea urchin eggs to release a signal for sperm to follow? Is this signal molecule likely to be a small or large molecule? Egg What happens at the sperm when a ligand is received? What happens to the sperm after it binds to the outer jelly coat layer of the oocyte? Y Peer Instruction Peer Instruction How does the oocyte protect itself against polyspermy? Vesicles full of carbohydrates Vesicles moved towards membrane High osmotic gradient Peer Instruction How does the oocyte protect itself against polyspermy? You may observe this in next week’s lab. Gene Mutated Normal location of the protein Fertilzation rate of mutant Other phenotype? Small protein from oocytes Released from oocyte 21.3% Fertilization in test tube is 100% “Bindin” receptor protein Exterior of sperm membrane 4.4% Sperm can pass jelly coat layer easily “Resact” receptor protein Exterior of sperm membrane 21.3% Fertilization in test tube is 100% Sperm-specific receptor protein Exterior of sperm membrane 8.5% Sperm on vitelline envelope fertilize well Fertilizin receptor protein Exterior of oocyte vitelline envelope 4.4% Sperm reach vitelline layer easily Jelly coat proteins Forming jelly coat layer on oocyte 8.5% No visible difference in oocyte layers Wild-type sperm and oocytes n/a 100% Sperm find oocyte and reach vitelline envelope layer quickly Peer Instruction Analyze this data. Blocking polyspermy, The Calcium Wave Blocking polyspermy, Fertilization Membrane Pulls Away This clears other sperm away from the plasma membrane by ~6 seconds after sperm entry Blocking polyspermy, the Fast block • The egg is still vulnerable to polyspermy in the first few seconds – Especially problematic with many sperm reaching the jelly coat at nearly the same time • The ‘Fast Block’ system uses the change in membrane potential in the egg to help protect against a second sperm – Change in membrane potential rapidly and temporarily distorts fertilizin structure – This inactivates all fertilizin molecules for ~6 seconds + + + + + + + - - - - - - + - + - + - + - + + - - - + - Cell-to-Cell Signaling • We’ve already talked about cell-to-cell signaling several contexts, – Growth factors, hormones, secreted proteins, etc • There is a vast array of cell signaling methods, which include – – – – – Lipid-soluble signals Cell-to-cell contact mediated by receptors Signal receptors Second messengers and enzymes Direct cytoplasmic contact –A quick tour is in order… Wednesday February 15th, 2017 Class 26 Learning Goals Determinants (case study: fruit fly ovary) Proliferation (case study: cleavage) Apoptosis (case study: caspase) Migration (case study: gastrulation) • After this class, you should be able to: • Propose several potential uses for cell proliferation, apoptosis or cellular migration in a developing organism • Predict a likely cleavage pattern based on adult body plan • Connect logical reasons for apoptosis to potential chemical cues by a cellular signaling pathway • Describe a gastrulating embryo in terms of movements of large numbers of cells Follicle cell Oocyte Nurse cell This is a confocal microscope image of an ovary inside of a female fruit fly. The oocyte, like a human oocyte, is supported as it grows by a number of surrounding cells. Peer Instruction Why is it advantageous for a mother’s cells to provide extra nutrients for an oocyte? How can this maternal determinant molecule give information to the new zygote that isn’t in the zygote DNA? When are maternally-provided molecules most useful? Early in development? Late in development? Why are paternal determinant molecules relatively rare? Peer Instruction In a few words: What is happening in this organism? Why is this early stage called ‘cleavage’? Besides development, where might we expect to find cell proliferation? Explain the mechanism of cleavage in each example. Radial cleavage: Example: Spiral cleavage: Discoidal cleavage: Peer Instruction Example: Example: Yolk Superficial cleavage: Example: Cells Yolk Un-separated nuclei Why would an adult multicellular organism intentionally destroy a few of its own cells? How does apoptosis help to develop the structure of this paw? Peer Instruction Peer Instruction Frog Gastrulation Ectoderm Mesoderm Endoderm Blastocoel Dorsal lip Cross section Blastopore Pre-Gastrulation Whole embryo Explain these cell movements. Initial Gastrulation Blastopore Frog Gastrulation Ectoderm Mesoderm Endoderm Presumptive gut Cross section Whole embryo What is happening here? Proliferation Apoptosis Migration Differentiation Signaling Thursday February 16th, 2017 Class 27 Learning Goals Abiotic Parasites • After this class, you should be able to: • Describe the important roles for genes and mechanisms in SINES, LINES, viruses and retroviruses • Predict the effect on viral survival of human mutations • Compare the timescales of abiotic parasite evolution, viral evolution, anti-viral human evolution, viral infection and viral entrance into a host cell Peer Instruction Transposons are small regions of a chromosome that happen to code for proteins that move that DNA to other regions of the chromosome. A mutation in a transposon causes increased production of similar transposons. Will evolution select for or against this mutation? How do transposons increase their population? Can transposons cause harmful mutations for the host? Peer Instruction How do Long Interspersed Nuclear Elements make new copies? Gene for reverse transcriptase Gene for integrase Cytoplasm “Parent” LINE Translation Transcription LINE protein LINE mRNA RNA polymerase Ribosome LINE mRNA and LINE proteins Reverse transcriptase Integrase cDNA Reverse transcriptase mRNA Integrase Original “parent” copy New copy Insertion of “Daughter” LINE How many of them are there? 98% similar Fraction of the genome made of transposons (or remnants of them): • Maize: 49-78% • Wheat: 68% 90% similar 75% similar • What does it means to say that viruses are: – Acellular – Obligate parasites – Diverse A bacterial cell (E. coli) How many genes does a circovirus have? Peer Instruction Circovirus ssDNA genome (1700 bp) What does the circovirus capsid gene encode? This bacteriophage has more genes than a circovirus. Every virion is heavier and more expensive. What advantage does this phage get from these genes? Peer Instruction Why is it worth it to the Ebola virus to spend energy to create envelope, matrix and nucleocapsid proteins? What parts of the Ebola virion give it the ability to specifically target human cells? Peer Instruction Explain how HIV infects a cell. Viral protein Enveloped virus Host protein Envelope (lipid bilayer) Genome (in this case, RNA) Capsid (protein) …about 10 billion virions produced daily Peer Instruction HIV has virion proteins that interact specifically with T-cell membrane proteins. Why is this advantageous for HIV? HIV increases transcription when T-cells are most active. Why is this advantageous for HIV? T-cell DNA: Activation TF P HIV Genome: Gag, Pol, Env P Viruses: Disease history • The last 1,000 years: – Smallpox and measles: High lethality destroyed colonized native cultures worthwide. – Influenza and common rhinoviral colds are likely to have killed more humans than any other cause • The past 100 years: – 1906: Viruses can cause cancer? – 1918: a new strain of influenza • killed >50 million people • was the most lethal combatant of WWI • reached almost every population in the world • – 1930s (and again in 2010s): polio outbreaks – 1970s: HIV The past 10 years: – SARS, avian flu and swine flu viruses threaten to make the jump from animals to humans to pandemic activity – Ebola • Current outbreak is largest on record & first North American case