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CALTECH APH 161 - Genes, Chromosomes and Genomes

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Slide 1Slide 2Slide 3Slide 4Cells Decide: What to Become, Where to GoYour Cellular Diversity: A Rogue’s GalleryGenes and Decisions: The Long Road from Mendel to MonodSlide 8Slide 9Red and White: Flies Eyes and the Nature of the GeneAn Unusual Ruler Led to the First Genetic MapThe Hershey-Chase Experiment and the Mechanism of Phage Genome DeliveryThe Structure of DNAThe Central Dogma of Molecular Biology: How Genes Lead to ProteinsHow Are Genes Related to What an Organism Is Like?Slide 16Genes and DNA: What Have We Learned?Chromosome Geography: Genomic vs. physical positionThe Immune SystemChromosome Geography in VibrioThe cylindrical bacteriumGenes, Chromosomes and GenomesGenes, Chromosomes and GenomesAPh/BE161: Physical Biology of the CellWinter 2009“Lecture 6”Rob Phillipsa, Snapshots of phase-contrast image showing cell F and its progeny and b, related bioluminescence image at different times t (given in days, a 24 h period of time) from the beginning of the measurement. Pixels in the bioluminescence images were binned 3 times 3 (pseudo-colour, where red is high signal intensity and blue is low signal intensity). Scale bar, 5 microm. c, The size of the cell F and all its progeny as a function of time measured from the phase-contrast images (non-binned pixels). The arrows point to the time where the snapshots in (a) and (b) were taken. d, The total number of pixels occupied by F and its all progeny versus time (black line) plotted in a logarithmic scale. The red line is the corresponding exponential growth fit: total size (t) = initial size times 2t/tau with tau = 23.04 plusminus 0.17 h. e, Density of bioluminescence for the same cell and all its progeny versus time. f, The average density of bioluminescence versus time (black line) and its fit (red line) with: left fenced(t)right fence = B + A cos(2pit/T0 + phi0). The resulting period is T0 = 25.4 plusminus 0.12 h, the initial phase phi0 = 52 plusminus 2.8°, the amplitude A = 12.9 plusminus 0.3 counts per pixel and the offset B = 14.8 plusminus 0.3 counts per pixel.Gene Expression in CyanobacteriaGene Expression in Cyanobacteria(Mihalcescu, Hsing, Leibler, Nature 2004)a, Upper part shows the phase-contrast snapshots of colonies A and B; lower part shows the related bioluminescence images. Scale bar, 5 microm. b, Normalized density of bioluminescence of individual cyanobacterial cells. Each colour corresponds to the progeny from one of the initial cells: red line, colony A; black line, colony B. c, Phase of individual oscillators as a function of their original colony and their evolution in time: red square, colony A; asterisk, colony B. An example of the exact location for three of the cells tracked and their phase evolution is shown, marked by the corresponding coloured lines: magenta, orange and purple. The change of the phase in time was quantified by a fit over a different period of time: the first 2 days (days 5–7), the entire time (days 5–10.5) and the last 2 days of the measurement (days 8.5–10.5). The fit function is left fenced(t)right fence = B + A cos(2pit/T0 + phi), with T0 = 24.78 h. The line segments in each graph, with corresponding colours, represent the resulting vector Pres = sumPi, where Pi is the unit vector whose orientation is the measured angle of the same colony cell i.Gene Expression in CyanobacteriaGene Expression in Cyanobacteria(Mihalcescu, Hsing, Leibler, Nature 2004)Figure 1 The photoperiodic response of long-day insects which are induced to enter diapause when the daylight hours falls below a certain level. The four species shown here, Laspeyresia molesta, Pieris brassicae, Acronycta rumicis, and Leptinotarsa decemlineata each leaves diapause when daylight is 14–17 hours. (After Danilevskii 1965). (From Gilbert, Developmental Biology)Diapause in InsectsDiapause in InsectsBombyx mori – diapause as early embryoClaim: even the protein by itself goes through two-week time evolution.http://centros.edu.aytolacoruna.es/iesadormideras/actividades/Paginamicroscopio/Bombyx%20_mori.htmlCells Decide: What to Become, Cells Decide: What to Become, Where to GoWhere to Go(Berman et al.)Embryonic DevelopmentImmune ResponseTwo very distinct examples of cellular decision making.Case study #1: differentiation of cells during development. Starting from an egg, one cell becomes many different types.Case study #2: decision of where to go. There are other decisions that represent the rapid response of cells.Your Cellular Diversity: A Rogue’s Your Cellular Diversity: A Rogue’s GalleryGallery(Berman et al.)As seen in the movie of the embryo, in multicellular organisms during development cells ``decide’’ to become different types.Diversity of cell types is enormous. You have over 200 cell types in your body.Big picture questions to ponder: how do cells decide, how are decisions implemented, how decisive? The answer came from an unexpected quarter: watching how cells decide what to eat.http://content.answers.com/main/content/wp/en/thumb/9/94/400px-Cell_differentiation.gifGenes and Decisions: The Long Genes and Decisions: The Long Road from Mendel to MonodRoad from Mendel to Monod(Berman et al.)Breeding experiments led Mendel to the abstract idea of genes as the unit of inheritance.Mendel examined the propagation of seven characters. He measured frequencies.At that point, no linkage to the physical idea of a chromosome.What is a gene? We now know that it is a particular part of a DNA molecule.The numbers: Seed shape: 5474 vs 1850Seed color: 6022 vs 2001Genes and Decisions: The Long Genes and Decisions: The Long Road from Mendel to MonodRoad from Mendel to MonodGenes and Physical Objects? A Genes and Physical Objects? A Parallel ThreadParallel ThreadStudying the structure of cells led to a recognition that during cell division, there was systematic segregation of certain parts of the cell.Red and White: Flies Eyes and the Red and White: Flies Eyes and the Nature of the GeneNature of the Gene(Berman et al.)``The insight that unified these three fields- heredity, evolution, and development- and set biology on the course toward its current success came only at the beginning of the twentieth century. It derived from the discovery that the gene, localized to specific positions on the chromosome, was at once the unit of Mendelian heredity, the driving force for Darwinian evolution, and the control switch for development.’’ -Eric KandelThomas Hunt Morgan and his gene hunters used flies as


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CALTECH APH 161 - Genes, Chromosomes and Genomes

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