Cellular Self-Organization

Question 1

Define symmetry breaking

Question 2

What properties does self-feedback product?

Answer 2

Robustness and bistability

Question 3

What properties does feedback between entities produce?

Answer 3

Spatio-temporal patterning

Question 4

What causes Turing patterns?

Answer 4

Reaction-diffusion of morphogens

Question 5

What does the Gierer-Meinhardt model show?

Answer 5

Diffusible inhibitor

a is a short-range autocatalytic substance = activator
h is its long-range antagonist = inhibitor.

Question 6

What is the limiting component of the diffusible inhibitor? ***

Answer 6

If activator inhibits the substrate, the substrate will be depleted

This occurs in cell polarity

Question 7

How do patterns appear?

Answer 7

Patterns emerge from homogeneous states
Different patterns can appear after partial ablation

Question 8

Define ultradian oscillation

Answer 8

Oscillations around 2-3hours

Question 9

What occurs under ultradian oscillations?

Answer 9

Developmental processes
Cell proliferation
DNA damage responses
Immune responses

Question 10

What is the relationship between p53 and mdm2?

Answer 10

Negative feedback loop

p53 causes transcription of mdm2
mdm2 inhibits p53 causing its degradation

Question 11

What is p53?

Answer 11

Transcriptional factor that regulates genes for repair and cell death/sensescence

Question 12

What is mdm2?

Answer 12

Ubiquitin-protein ligase

Question 13

What type of oscillations does p53 show?

Answer 13

Sustained oscillations that are out of phase with mdm2

Question 14

How can noise affect oscillations?

Answer 14

Noise can prevent oscillations from damping out

Noise-induced oscillations produce variable amplitudes, which increase with noise strength

Question 15

What is a segmentation clock?***

Answer 15

The vertebrate segmentation clock is a molecular oscillator that regulates the periodicity of somite formation.

Three signalling pathways have been proposed to underlie the molecular mechanism of the oscillator, namely the Notch, Wnt and Fgf pathways.

Question 16

What is the Hes gene and its alternate names?

Answer 16

Hairy and Enhancer of Split-1 = in mammalian systems (Her in zebrafish)

Hes genes are downstream targets of the Notch pathway that encode transcriptional repressors.
These repressors are likely to establish negative feedback loops by repressing their own transcription,

Question 17

What is Hes7 and its roles?

Answer 17

Repressive transcription factor that targets its own promoter

Essential for somitogenesis and neurogenesis

Question 18

What is Cdc42?

Answer 18

GTPase regulator of cell polarity and morphogenesis in eukaryotes

GTPases are activated by GEF, allowing GDP to dissociate and GTP to bind

Question 19

What is the role of Cdc42?

Answer 19

GTPase causing activation of WASP and resulting in actin polymerization

Allowing, in this case, yeast to chagne orientation

Question 20

What is FRAP?

Answer 20

Fluorescence recovery after photobleaching

Question 21

What does FRAP show in terms of Cdc42?

Answer 21

FRAP gives a measure of kinetics of protein diffusion and binding

Showing Cdc42 has a fast turnover at memrbane site

Question 22

What doe LatA do?

Answer 22

Blocks actin filament assembly

Question 23

What are Bem-1 and F-acting requried for?

Answer 23

Polarity

Bem-1 = GEF
F-actin = part of cytoskeleton

Question 24

What happens with overexpression of Bem1-GEF or Cdc42 GEF?

Answer 24

Leads to multiple dynamic clusters in yeast = too many budding sites per cell

Question 25

What does parallel positive feedback by Bem1 and F-acin cause in Cdc42?

Answer 25

Both would lead to overexpression of Cdc42

Question 26

What is the outcome of positive feedback on cell polarity?

Answer 26

Leads to robust generation of cell polarity, which is an example of symmetry breaking

Question 27

What does E.coli allow us to study?

Answer 27

Useful model system for PROTEIN OSCILLATION

Question 28

How is a standing wave produced?

Answer 28

When two waves are travelling towards each other in opposing direction They produce a standing wave, which only moves up and down not left to right

Question 29

What proteins show oscillations in E.coli?

Answer 29

Min proteins

Question 30

What is the role of FtsZ ring?

Question 31

What is the role of MinC?

Answer 31

Inhibits formation of FtsZ ring

Question 32

What is the role of MinD?

Answer 32

ATPase that when bound to ATP attaches to membrane MinC binds MinD forming MinCD complex, which oscillates from pole to pole inhibitng FtsZ ring formation at poles

Question 32

What is the role of MinE?

Answer 32

MinE regulates activity of MinD = promotes disassembly of MinCD complex at cell poles and centre

Question 33

Describe the feedback loop between minD and minE

Answer 33

MinD is autoactivated MinD activates MinE MinE has a delayed inhibition of MinD

Question 34

What is chemotaxis?

Answer 34

This is the movement of an organism or cell toward or away from a soluble chemical stimulus

Question 35

What is haptotaxis?

Answer 35

The directed movement of cells in response to a gradient of adhesion molecules or other surface-bound cues = immobilized chemicals

Question 36

What is durotaxis?

Answer 36

Cells move in response to differences in the mechanical stiffness or rigidity of their substrate. Softer materials might be found in areas undergoing tissue repair, while stiffer materials could be associated with more mature tissue. Cells form attachments to their substrates through structures called focal adhesions. On stiffer surfaces, cells can form stronger focal adhesions, leading to increased traction forces that enhance their ability to move.

Question 37

What are the regions of cytoskeleton polarization?

Answer 37

Front = actin polymerization Back = myosin contraction

Question 38

What are filopodia and how are htey formed?

Answer 38

Filopodia are slender, finger-like projections that extend from the leading edge of a migrating cell. They are formed by the polymerization of actin filaments, activated by Cdc42

Question 39

What are lamellipodium?

Answer 39

Lamellipodia are broad, sheet-like extensions formed at the leading edge of migrating cells. They arise from the polymerization of a branched network of actin filaments, largely regulated by the Arp2/3 complex, which is activated by Rac.

Question 40

What are stress fibres?

Answer 40

Stress fibres are contractile bundles of actin filaments, often composed of a thicker array of actin filaments along with myosin motor proteins Facilitated by Rho

Question 41

Which signalling pathway do Hem-1 and WAVE/SCAR act in?

Answer 41

Act downstream of Rac1 Specifically involved in actin dynamics and the formation of lamellipodia

Question 41

What are focal adhesions and their role?

Answer 41

Focal adhesions are complex structures formed at the points where the cell membrane adheres to the extracellular matrix. They develop as a result of interactions between integrin receptors on the cell surface and the extracellular matrix components. Facilitated by Rho

Question 42

What is Hem-1?

Answer 42

Hem-1 is a key component of the WAVE complex Upon activation by Rac1, Hem-1 helps stabilize and promote the assembly of the WAVE complex at the leading edge of the cell.

Question 43

What is the role of WAVE/SCAR?

Answer 43

When Rac1 is activated it binds WAVE/SCAR. Hem-1 facilitates the interaction between Rac1 and the WAVE complex. WAVE/SCAR comlex are activators of Arp2/3 = leading to enhanced activation of the Arp2/3 complex

Question 44

How is actin polarization explained by negative feedback loops?

Answer 44

Nucleation-promoting factor and negative feedback from actin filaments generates spontaneous polymerization waves

Question 45

What happens to Hem-1 waves at mechnaical barriers?

Answer 45

Waves are extinguished Tension in the cytoskeleton changes, which can lead to Rho activation and Rac inhibition