Final Flashcards

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1
Q

_______ is necessary to maintain tissue function

A

Cell Renewal

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2
Q

What cell types are capable of re-entering the cell cycle and replacing damaged/lost cells?

A

fibroblasts and endothelial cells

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3
Q

Describe why cell renewal is necessary to maintain tissue function

A

Most somatic cells are arrested in G0 and do not proliferate

Cells in tissues may be lost due to DNA damage, injury, apoptosis etc.

New cells must replace these damaged/dead cells in the tissue – cell renewal

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4
Q

What is endothelial cell proliferation is driven by?

A

The growth factor VEGF

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5
Q

What can damage to endothelial cells/blood vessels lead to?

A

Hypoxia – tissue is not receiving enough oxygen

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6
Q

What does tissue hypoxia promote?

A

vascular endothelial growth factor production (VEGF) secretion, which in turn promotes endothelial cell proliferation through RTK signaling

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7
Q

What do endothelial cell do in response to VEGF?

A

Endothelial cells proliferate and form new capillaries (angiogenesis), which innervates the hypoxic tissue with new blood vessels

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8
Q

Describe the four stages of Wound healing

A
  1. Hemostasis
  2. Inflammation
  3. Proliferation
  4. Remodeling
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9
Q

Describe the four stages of wound healing

A

Hemostasis – cessation of blood flow: blood vessels constrict to minimize blood flow/loss, platelets promote clot formation, fibrin (fibrous protein) cross links platelets in clot

Inflammation – immune cells travel from bloodstream to wound site, fluid build up and immune cell extravasation promoted by vasodilation of blood vessels (swelling), increasing blood flow (redness)

Proliferation – fibroblasts enter wound site and secrete ECM components including collagen, rebuilding lost ECM. Epithelial cells continue to proliferate and close wound, myofibroblasts help pull damaged tissue together, new blood vessels form to innervate newly formed tissue through angiogenesis

Remodeling – collagen fibers are remodeled (type III to type I), new epithelium is fully formed and scar tissue forms

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10
Q

What do fibroblasts differentiate into?

A

A specific subtype of fibroblast called the myofibroblast

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11
Q

When do myofibroblasts form?

A

Myofibroblasts form from differentiation of fibroblasts during wound healing

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12
Q

What do myofibroblasts do?

A

Myofibroblasts are contractile cells that promote wound healing by pulling damaged tissue together using smooth muscle type actin and myosin during the proliferation phase

This differentiation process is driven by mechanical tension and the cytokine transforming growth factor-β1 (TGF-β1)

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13
Q

What is the average lifespan of the human liver cells?

A

200-300 days

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14
Q

Describe two aspects of liver regeneration

A
  1. Liver cells are arrested in G0 but capable of re-entering cell cycle
  2. Liver regeneration is done by normal differentiated liver cells in response to specific extracellular signals
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15
Q

Describe a fact about rat liver removal

A

In rats, surgical removal of 2/3 of the liver leads to full regeneration of liver in a few days

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16
Q

What are most cells in adult tissues are replaced by?

A

The proliferation and differentiation of stem cells

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17
Q

Define stem cells

A

Stem cells - undifferentiated cells with the potential for self renewal and differentiation

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18
Q

What are stem cells capable of?

A

Stem cells are capable of asymmetric cell division, producing one stem cell and one differentiating cell through mitosis (can also produce two stem cells through mitosis)

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19
Q

What are trasit-amplifying cells?

A

undifferentiated cells in transition from stem to differentiated cell

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20
Q

Define differentiation

A

process of becoming a specialized cell type – involves large changes in gene expression (epigenetics, chromatin remodeling), also changes in cell morphology, metabolism etc.

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21
Q

What is a hematopoietic stem cell (HSC)?

A

a classic model of a self-renewing stem cell that gives rise to a multitude of differentiated cell types

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22
Q

Describe the different types of blood cells

A

Erythrocytes – red blood cells, transport oxygen and CO2

Platelets – fragments of megakaryocytes that promote clot formation

Macrophages – phagocytic cells involved in both innate and adaptive immunity

Granulocytes – white blood cells with immune functions, characterized by secretory granules

B and T lymphocytes (B cells and T cells)– white blood cells involved in adaptive immune response

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23
Q

How many blood cells does the human body produce in a day?

A

100 billion

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24
Q

What does the maintenance of blood cell populations depend on?

A

Adult blood cells do not proliferate – maintenance of cell populations depends on hematopoietic stem cell population maintenance

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25
Q

What do all of the different types of blood cells develop from?

A

hematopoietic stem cells in the bone marrow

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26
Q

What makes bone marrow transplants possible?

A

The vast potential of HSCs

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27
Q

What are some of the most proliferative stem cells in the body?

A

Intestinal crypt stem cells

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28
Q

What is the lifespan of the intestinal epithelium?

A

A few days, exposed to harsh environment, billions of cells shed each day

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29
Q

What replaces lost epithelial cells in the intestines?

A

Stem cells at the base of intestinal crypts continually divide and replace lost epithelial cells

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30
Q

What makes up 2/3 of the intestinal crypts?

A

Transit amplifying cells

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31
Q

What is a niche?

A

An extracellular environment that maintains stem cells

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32
Q

Stem cells reside within specific microenvironments called _______

A

niches

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33
Q

What do niches provide?

A

provides environmental signals that maintain stem cells/balance their self renewal and differentiation

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34
Q

In the intestinal crypt, what helps maintain intestinal crypt stem cells?

A

Paneth cells and Wnt-producing fibroblasts secrete Wnt polypeptides that help maintain intestinal crypt stem cells

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35
Q

Describe the several stem cell compartments of mammalian skin

A

Epidermal stem cells differentiate into transit-amplifying cells, which differentiate into new epidermis cells

Bulge stem cells give rise to transit-amplifiying matrix cells, which differentiate and form the hair shaft

Sebaceous gland stem cells maintain the sebaceous gland, which secretes oils to protect the skin

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36
Q

What is the muscle stem cell?

A

The satellite cell

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37
Q

Describe stem cells in the skeletal muscle

A

Satellite cells – stem cells in muscles located beneath basal lamina of muscle fibers

The progeny cells of satellite cells differentiate and fuse into new muscle fibers

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38
Q

True or False: Skeletal muscle is capable of rapid regeneration in response to damage (injury, exercise)

A

True

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39
Q

Embrionic stem cells are _______

A

totipotent: able to give rise to all tissues

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40
Q

Give the hierarchy of stem cell differentiation ability

A

Totipotent > Pluripotent > Multipotent

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41
Q

what kind of state are embryonic stem cells grown in?

A

An undifferentiated state.

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42
Q

Embryonic stem cells can be induced to form ______ and then differentiate into a variety of cell types.

A

embryoid bodies

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43
Q

Describe Somatic cell nuclear transfer and cloning

A
  • Nuclei from adult somatic cells are transferred to enucleated oocyte
  • 1-2% of embryos generated give rise to adult with identical genetics (clone)
    - Epigenetic reprogramming necessary to give
    rise to all cells in clone
    - Limited lifespan
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44
Q

Describe Therapeutic cloning

A
  • Similar process (adult somatic cell nuclear transfer)
    could be utilized for therapeutic cloning
  • Generation of clonal embryonic stem cells
  • Stem cells could then be differentiated in vitro to
    give rise to cells and tissues for transplant
    - Identical genetics – no risk of
    transplantation rejection
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45
Q

What TF are able to reprogram somatic cells to a pluripotent state?

A

A cocktail of transcription factors termed the Yamanaka factors

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46
Q

Describe how we are able to reprogram somatic cells to a pluripotent state

A
  • A cocktail of transcription factors, termed the Yamanaka factors, are able to reprogram somatic cells to a pluripotent state.
  • This allows adult fibroblast cells to be “reprogrammed” into induced pluripotent stem cells through the expression of specific transcription factors.
  • Takashi and Yamanaka introduced Oct4, Sox2, Klf4, and c-Myc transcription factors through a retroviral vector which infects the somatic cell.
  • An induced pluripotent stem cell is then produced, which functions similar to embryonic stem cells – capable of differentiating into all cell types.
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47
Q

How do Yamanaka factors work?

A

They act synergistically to repress differentiation genes and open chromatin and activate transcription of pluripotency genes.

  • Yamanaka factors form a positive feedback autoregulatory loop that maintains pluripotency in both induced and embryonic stem cells
  • The function of these transcription factors activates transcription of pluripotency-promoting genes and represses expression of differentiation genes
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48
Q

What is c-Myc?

A

A proto-oncogene that promotes proliferation of stem cells – can lead to risk of tumor development following stem cell implantation

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49
Q

What was found to be dispensable in the production of induced pluripotent stem cells?

A

Nanog

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50
Q

What is Transdifferentiation?

A

The direct conversion of cells from one fate to another.

The direct differentiation of a differentiated adult cell into another differentiated lineage

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51
Q

True or false: Differentiated blood cells can also transdifferentiate to other blood cell types, but NOT hematopoietic stem cells

A

False: they CAN transdifferentiate into HSCs

(ex: leukocyte can go to granulocyte; leukocyte CAN ALSO go to hematopoietic stem cell)

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52
Q

How can transdifferentiation occur?

A

Through mutations accumulated in cancer cells i.e. leukemia, lymphomas.

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53
Q

What is the extracellular matrix (ECM)

A

A network of proteins, polysaccharides, and other components that fills the spaces between cells and binds cells and tissues together

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54
Q

Where is ECM most abundant?

A

In connective tissues – tendons, bones, cartilage

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55
Q

What is the basal lamina?

A

A thin sheet of ECM that supports epithelial cells, also surrounds muscles and peripheral nerves

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56
Q

What is ground substance?

A

Fibrous proteins embedded in a gel-like matrix of polysaccharides that makes up the ECM

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57
Q

What are fibroblasts?

A

Specialized cells that secrete ECM

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58
Q

What are chondrocytes?

A

Chondrocytes secrete collagen and other extracellular matrix components to form and maintain cartilage

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59
Q

What is the most abundant ECM protein?

A

collagen

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60
Q

What kind of structure does collagen form?

A

Individual collagen polypeptides wind together forming a triple helical structure resembling a rope

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61
Q

What does the triple helix domain of collagen contain?

A

It contains regular G(glycine)-X(often proline)-Y(often hydroxyproline) repeats to allow for tight packing (glycine required in every 3rd position)

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62
Q

What is Hydroxyproline

A

A modified proline residue formed in the ER lumen

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63
Q

True or false: Collagen helices are stratified and cross linked into fibrils

A

True

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64
Q

What do Fibrils help contain?

A

The gaps between collagen triple helices that contribute to flexibility

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65
Q

Do fibrils form inside the cell?

A

No, Fibrils do not form within cells – procollagen is cleaved to collagen following secretion from the cell

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66
Q

What has has regular breaks in its helical domain?

A

Type IV Collagen

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67
Q

Describe Type IV collagen

A

Type IV collagen forms networks rather than fibers – key role in formation of basal lamina

G-X-Y domain in helical region is interrupted by nonhelical domains – cannot form fibers

Type IV collagen is more flexible than fiber-forming collagens

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68
Q

What is the makeup of a Glycosaminoglycan (GAGs) ?

A

repeated disaccharide chains which often contain sulfate groups

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69
Q

Where are GAGs formed?

A

The golgi

70
Q

What do GAGs do?

A

GAGs help form a hydrated gel-like network in the extracellular matrix

GAGs often possess sulfate modifications which confer a negative charge – interact with positively ions and water molecules

71
Q

What is the significance of Hyaluronan?

A

It is is the only GAG that forms long chains, all others are linked to proteins to form proteoglycans

72
Q

What are Proteoglycans?

A

core proteins with numerous GAG chains

Proteoglycans contain many (over 100) GAG chains, each consisting of up to 100 sugar residues

Different GAG modification confer variable properties to different proteoglycans – highly diverse

73
Q

What is Fibronectin?

A
  • A functional scaffold connecting multiple ECM elements.
  • An adhesion protein secreted primarily by fibroblasts
  • Contains multiple binding sites that link ECM components to one another and to cells
  • A dimer composed of two long (~2500AA) chains crosslinked by disulfide bonds
74
Q

What do adhesion proteins do?

A

link components of the ECM to one another

75
Q

What are lamins?

A
  • Adhesion proteins that are the principal component of the basal lamina
  • T-shaped heterotrimeric proteins that can link together with one another to form extensive networks
76
Q

What can Laminins interact with?

A

cell surface proteins (integrins), proteoglycans, and other adhesion proteins like nidogens

77
Q

What are integrins?

A

Integrins are cell surface receptors that bind to ECM proteins, linking cells to the ECM

  • heterodimeric proteins containing an alpha and beta subunit
  • The alpha subunit binds to divalent cations (Mg2+, Ca2+) – regulates ligand/matrix binding
  • 18 different alpha subunits + 8 different beta subunits – 24 different integrin complexes in humans
78
Q

How are integrins are connected to the cytoskeleton?

A

via focal adhesions or hemidesmosomes

  • Focal adhesions link intermediate filaments to the extracellular matrix – stable connections
  • Focal adhesions link actin microfilaments to the extracellular matrix – less stable than hemidesmosomes
79
Q

What are cell adhesion molecules are capable of?

A

highly selective homophilic (like with like) and heterophilic interactions

Certain adhesion molecule interactions form stable structures (adherens junctions, hemidesmosomes), others are transient

80
Q

What is the immune response to pathogens is mediated by?

A

By the extravasation of leukocytes (white blood cells) from the bloodstream to sites of inflammation/infection

81
Q

What do Selectins do?

A

mediate transient interactions between leukocytes and endothelial cells that line blood vessels

82
Q

What do L-selectins on leukocytes bind to?

A

carbohydrates on the endothelial cell surface.

This represents a weak initial adhesion event that facilitates stronger integrin-ICAM (intercellular adhesion molecules) adhesions

83
Q

What does the firm adhesion between leukocytes and endothelial cells allow for?

A

leukocytes to squeeze between endothelial cells and migrate into tissues

84
Q

What are adherens junctions and desmosomes?

A

stable adhesions mediated by cadherins

85
Q

What do adherins junctions do?

A

junctions link the actin cytoskeleton (microfilaments) of adjacent cells together and form adhesion belts

86
Q

What do desmosomes do?

A

link intermediate filaments of adjacent cells together

87
Q

Where do tight junctions form?

A

between strands of transmembrane proteins and separate the apical and basolateral domains

88
Q

What do tight junctions prevent?

A

fluid and ion flow between cells – strong seals but weak adhesive strength, often associated with other junctions

89
Q

What makes the most apical junctions on epithelial cells?

A

Tight junctions

90
Q

What do gap junctions form?

A

a porous connection between cells

Gap junctions form direct connections between adjacent cells – share cytoplasmic components less than 1000 daltons in size (cAMP, Ca2+)

91
Q

Describe the structure of a gap junction

A

Gap junctions are dodecameric (12 subunits) channels formed through the interactions of hexameric (6 subunits) connexons on adjacent cells

92
Q

describe the structure of a connexon

A

Six connexins joined together

93
Q

True or False: Gap junctions are dynamically regulated and can exist in open and closed conformations

A

True

94
Q

True or false: A number of congenital diseases are due to defects in gap junctions

A

True

95
Q

What are Plasmodesmata? Describe some of their characteristics

A

junctions in plant cells that have analogous functions to gap junctions

Due to cell walls, plant cells do not require cytoskeletal adhesions form stable associations with one another

Projection of smooth ER often found in plasmodesmata pore

Dynamically regulated similar to gap junctions (open/close)

96
Q

What type of organisms are commonly used in research?

A

GMOs

  1. fruit fly
  2. c. elegans
  3. fish
  4. mouse
97
Q

Describe some advantages and disadvantages to using drosophila as GMOs

A

Advantages:
Large community of researchers
gold standard in genetic tools
short generation time

Disadvantages:
Limited behavioral repertoire
Fewer shared genes with humans compared to rodents

98
Q

What was the 2nd multicellular organism to have their genome sequenced?

A

drosphila

99
Q

Describe some advantages and disadvantages to using mice as GMOs

A

Advantages:
- Really only mammalian model with well developed
genetic tools.
- Wide behavioral repertoire.
- Share many genes and pathways with humans:
applicability to human disease

Disadvantages:
- Significantly more difficult (and costly) to house than
most the other transgenic models.

100
Q

Define a genetically modified mouse

A
  • A mouse that has had its genome altered through the use of genetic engineering techniques.
101
Q

What is the most commonly used organism for GMOs

A

Mice
- used for research or as animal models of human diseases
- also used for research on genes and genetic pathways.

102
Q

How can we study the function of genes expressed throughout various tissues in an organism?

A
  • Removing genes (knockouts)
  • Expressing transgenes
    - Marking cells that express a gene or are active
    - Reducing gene expression (RNA interference)
    - Activating or inhibiting cellular populations
    experimentally
103
Q

What is a knockout?

A

removal/inactivation of specific gene

104
Q

How can knockouts can provide information about a gene’s function?

A

Comparing knockout and wild-type phenotypes can provide information on the knockout gene’s function

105
Q

Give an example of a knockout

A

Leptin knockout

  • fat mouse
  • Removing leptin stops the mouse from feeling satiated
106
Q

Describe the steps to making Genetically Engineered Mice through Homologous Recombination

A
  1. Make a DNA construct where gene of interest is
    interrupted by a “marker” or selector gene
    neo – Neomycin resistance gene is often used
  2. Electroporate DNA construct into cultured
    embryonic stem cells (ES)
  3. Allow Homologous recombinationto take place
    • Homology arms – long segments of genomic DNA
      flanking the sequence to be inserted that
      facilitate recombination
    • Homologous recombination - LOW FREQUENCY
      EVENT
  4. Select cells that incorporated marker
  5. Inject stem cells into mouse blastocyst and implant
    into foster mother mouse
  6. Mice homozygous for mutated gene (knockout) can
    be obtained through mating
107
Q

Describe how “Knock in” mice can be generated

A

Can be generated through the same techniques

  • Gene to be “knocked in” flanked by homology arms
  • Homologous recombination will lead to the
    incorporation of gene to be “knocked in” at the
    location of homology arm sequences in genome
108
Q

What are humanized mice

A

Mice where certain genes have been replaced with homologous human gene

109
Q

What does CRISPR allow for?

A
  • Specifically targeted alterations as small or as large
    as needed
  • Circumvents the “randomness” of mutations and
    homologous recombination
  • Makes anything a “model system” because only a
    small part of the genome needs to be known
110
Q

What is Cas9?

A

Cas9 – “CRISPR associated protein”, nuclease that acts as the “scissors”

111
Q

What does Single guide RNA (sgRNA) do?

A

It targets specific gene sequence in genome

  • Nucleotides in guide RNA are complementary to
    nucleotides in DNA sequence
112
Q

Describe DNA editing using CRISPR-Cas9

A
  • Two DNA sequences introduced to cell
    - One codes for Cas9 protein
    - Other codes for sgRNA
  • Cas9 can only digest DNA near protospacer adjacent
    motif (PAM) sites (NGG)
  • sgRNA contains 20bp sequence specific for sequence
    in genome immediately 5’ to endogenous PAM site
113
Q

Describe how CRISPR-Cas9 can be used to knock out and knock in genes

A

Double stranded breaks can be repaired through
two mechanisms

  • Non-homologous end joining (NHEJ) – broken DNA
    ends are rejoined, often includes insertion or
    deletion
    - Frameshift resulting from indel often leads to
    premature stop codon
  • Homology-directed repair (HDR) – DNA construct
    with homology arms is used as a template for
    homologous recombination
114
Q

Describe how you can generate knockouts/knock-ins in Mice through CRISPR

A
  • A guide RNA (sgRNA) is designed to target a specific
    sequence in the gene of interest.
    -The sgRNA is complementary to the DNA
    sequence near the gene’s coding region.
  • The CRISPR-Cas9 system, which consists of the Cas9
    protein (which cuts DNA) and the sgRNA (which
    guides Cas9 to the target site), is introduced into
    either the mouse embryonic stem cells (ESCs) or
    fertilized eggs.
  • The Cas9 protein then creates a double-stranded
    break at the target site in the genome.
  • This break triggers the cell’s DNA repair mechanisms,
    typically via non-homologous end joining (NHEJ).
  • After CRISPR editing, the cells or embryos are
    screened for successful gene disruption.
  • If embryos are used, they are implanted into a
    surrogate mother, and the mice that carry the
    knockout allele in their genome are bred to establish
    a knockout lineage.
115
Q

How was RNAi-mediated mRNA degradation first discovered?

A
  • Phenomenon first described after injecting single-
    stranded RNAs into petunias to alter flower color
    -Inexplicably led to loss of color…
  • Similar observation described by Craig Mello and
    Andrew Fire in C. elegans.
  • They showed that a dsRNA (with sequence region of
    mRNA) potently induced the degradation of that
    mRNA.
  • Antiviral response; new paradigm for gene
    regulation
116
Q

How does RNA interference with siRNA reduce expression of a target gene?

A
  • RNAi allows researchers to lower or “knock down”
    target gene expression without removing the gene
    from the genome. (KNOCK DOWN not REMOVE)
  • dsRNA (natural or artificial) is cleaved by the
    endonuclease Dicer.
  • The RISC complex is then recruited to siRNA duplex,
    which unwinds to form ssRNA.
  • The RISC complex then scans to find mRNA which is
    complementary to associated ssRNA.
  • Once found, a component of RISC cleaves the mRNA,
    leading to its degradation and ultimately a reduced
    expression of whatever gene it encoded.
117
Q

Describe the makeup of microtubules?

A

polar, hollow filaments made of two subunits

Microtubules are formed through dimeric associations of alpha and beta tubulin

These dimers assemble into ring-shaped, hollow filaments approximately 25nm in diameter (actin microfilaments – 7nm)

118
Q

Alpha and beta tubulin are _______

A

obligate heterodimers

119
Q

Describe the obligate heterodimer of alpha and beta tubulin?

A

Tubulin dimers form shortly after protein synthesis – obligate heterodimers

Alpha and beta tubulin bind to GTP/GDP which influence their association dynamics.

Beta tubulin has GTPase activity;alpha tubulin does not

120
Q

MTs have a fast growing ___ end and a disassembling ____end

A

plus, minus

121
Q

What is added the plus end of microtubules?

A

GTP bound tubulin dimers are added to the + end of microtubules

122
Q

What disassociates from the minus end of microtubules?

A

GDP bound tubulin dimers dissociate from the - end of microtubules

123
Q

How can a a GTP cap form?

A

If GTP-tubulin dimers are rapidly added to the + end

124
Q

What does a GTP cap influence?

A

The presence of a GTP cap at the plus end will influence growth/shrinkage kinetics – prevents catastrophe

125
Q

Where are minus ends usually anchored?

A

at the centrosome or microtubule organizing center (MTOC)

126
Q

Describe the factors that influence dynamic instability

A

Microtubule plus ends will grow as long as new GTP bound tubulin dimers are added faster than GTP is hydrolyzed within the tubule

Minus ends are usually anchored at the centrosome or microtubule organizing center (MTOC) to prevent depolymerization

Microtubule shrinkage will occur at the plus end if GTP hydrolysis occurs more rapidly than GTP bound tubulin dimers are added to the tubule

127
Q

How are Microtubule growth and shrinkage dynamically regulated?

A

Microtubule-associated proteins (MAPs)

Microtubule polymerases bind to the + end and increase the incorporation of GTP bound tubulin heterodimers by ~10 fold

128
Q

Give an example of a catastrophe factor

A

Microtubule depolymerases are a class of MAPs that bind to the plus end and accelerate the dissociation of GTP-bound tubulin dimers from the + end, leading to the loss of the GTP cap and promoting catastrophe

129
Q

Give an example of a rescue factor

A

Other MAPs (CLASPs), bind to microtubules undergoing catastrophe and prevent further depolymerization, also promote rescue (sudden switch back to growth)

130
Q

What are the two primary microtubule organizing centers (MTOC) in the cell

A

the centrosome and basal body

Centrosomes are the primary MTOC in animal cells – basal bodies are nucleation sites for MT associated with cilia and flagella

131
Q

What do Microtubule organizing centers do?

A

They nucleate new microtubules and serve as an anchoring site for microtubule minus ends – preventing minus end disassembly

132
Q

When are centrosomes duplicated?

A

during the G1/S transition in mitosis

133
Q

What is the core of the centrosome?

A

The centriole

134
Q

What does each centrosome contain?

A

two centrioles organized perpendicularly from one another

135
Q

Describe the structure of a centriole

A

cylindrical structures composed of 9 microtubule triplets arranged in a circle/ring

136
Q

True or false: Centrioles are not found in basal bodies

A

False. They are found in basal bodies

137
Q

What is gamma tubulin and where is it found?

A

– tubulin species that nucleates microtubule assembly – forms gamma tubulin ring complex from which microtubule filaments “grow”
- found in the centrosome

138
Q

What surrounds each centriole, what does it contain, and how does it function?

A

Pericentriolar material surrounds each centriole – contains gamma tubulin and functions as nucleation site for microtubule assemble

139
Q

What are the two families of motor proteins are associated with microtubule filaments

A

kinesins and dyneins

Both families of motor proteins couple ATP hydrolysis to conformational changes in the motor protein, generating motion and force

140
Q

What end of transport are each of the two families of motor proteins are associated with

A

Kinesins are responsible for plus end directed transport along the microtubules

Dyneins are responsible for minus end directed transport

141
Q

What are the two types of dyneins and what do they control?

A
  • Axonemal dyneins drive the motion of cilia
  • cytoplasmic dyneins control vesicle/cargo transport
142
Q

What are neuronal extensions are powered by

A

microtubule transport

143
Q

How are Microtubules in axons organized

A

with minus ends facing cell body, plus ends facing axon terminus

144
Q

How are Microtubules in dendrites organized?

A

bidirectionally

145
Q

How are microtubules in dendrites and axons stabilized?

A

MAPs. MAP2 stabilizes dendritic microtubules, tau stabilizes axonal microtubules

146
Q

What can form aggregates and tangles associated with neurodegenerative diseases?

A

Tau

147
Q

What relies on microtubules for structural support and trafficking?

A

Dendrites and axons on neurons

148
Q

How do Dynein and kinesin motors work to move organelles and vesicles?

A

In parallel.

Kinesins and dyneins combine to allow for bidirectional transport along microtubule filaments

Kinesins drive plus end directed transport

Dyneins drive minus end directed transport

149
Q

Chromosome separation during mitosis requires ________

A

microtubules and motor proteins

Movement of spindle poles is mediated by molecular motors – kinesins (+) and dyneins (-)

150
Q

Microtubules are highly associated with the ____

A

endoplasmic reticulum – vesicles originating in the ER for secretory pathway travel along microtubules

151
Q

What helps extend ER to periphery of cell

A

microtubules

152
Q

True or false: Microtubule associated motors are also responsible for positioning the ER (and other organelles) within the cell

A

True

153
Q

What are two Specialized MT structures?

A

Cilia and flagella

154
Q

Describe the two types of cilia

A

Primary cilia – sensory projections – contain receptors to detect extracellular signals

Motile cilia – cell movement

Both primary and motile cilia contain nine doublets of microtubules

155
Q

Describe flagella

A

Flagella – long, threadlike extensions responsible for movement through whip-like motion

156
Q

Where are cilia and flagella found

A

The plasma membrane

157
Q

What do primary cilia lack?

A

dyenins

158
Q

What do Motile cilia contain?

A

An extra central pair of microtubules as well as nexin proteins linking outer doublets together. Dynein motors are responsible for movement of outer doublets.

159
Q

What is the radial spoke

A

A protein complex connecting the central pair and outer doublets of microtubules

160
Q

What are both primary and motile cilia anchored to?

A

Basal bodies, which contain triplet microtubules and function as a MTOC

161
Q

What is cilia movement coordinated by?

A

Dynein movement

The movement of dyneins linking outer doublets of microtubules together causes bending of microtubules and cilia movement

162
Q

What are Intermediate filaments?

A

A diverse set of filament forming proteins

163
Q

True or false: Intermediate filaments oligomerize from dimers and create polar filaments

A

False.

Yes, they oligamerize from dimers, but no, they do not create polar filaments.

164
Q

How do intermediate filaments assemble?

A

High amount of diversity among intermediate filament proteins (size, AA sequence), but mechanism of assembly is similar

Monomers assemble into dimers through coiled-coil interactions

Dimers form tetramers through antiparallel interactions. These tetramers can join to form higher order oligomers

As both ends of intermediate filaments are the same, there is no polarity associated with intermediate filaments – no plus or minus ends

Intermediate filaments also do not have preferential assembly at each end – subunits can be exchanged along the length of the filament

165
Q

What are the primary intermediate filament found in epithelial cells

A

keratins.

Keratin is also the primary component of hair, skin, and fingernails

166
Q

What are desmosomes?

A

junctions between cells that adhere cells to one another

167
Q

What are plakins?

A

The site of intermediate filament (keratin) attachment on a desmosome. They typically form a dense plaque on the face of the desmosome.

168
Q

What do cadherin proteins do?

A

Cadherin proteins (desmoglein and desmocollin) link adjacent cells to one another

169
Q

What do hemidesmosomes do?

A

Hemidesmosomes anchor the cell to the extracellular matrix, linking cell surface integrin proteins to intermediate filaments through plectin

170
Q

What forms connections to other cytoskeletal systems?

A

Intermediate filaments

171
Q

What also forms links between intermediate filaments to actin microfilaments and microtubules

A

plectin

172
Q

What has important functions in tissue integrity?

A

Intermediate filaments like keratin