CMP Robustness and Adaptation PDF

Robustness - overview Robustness = the ability of a cell to maintain performance and function in the face of internal external pertubations. Redundancy = many genes and aspects of cells and organisms are replicated and have 'back ups', which are redundant when everything is healthy and ope...

Robustness - overview Robustness = the ability of a cell to maintain performance and function in the face of internal external pertubations. Redundancy = many genes and aspects of cells and organisms are replicated and have 'back ups', which are redundant when everything is healthy and operating correctly, but aid survival when there are abnormalities (e.g. many types of collagen, although type I accounts for 90% of collagen, if this is not made/incorrect then it can be substituted for by the previously 'redundant' types). Robustness – high temperatures Fever during infection can help the immune response by: o Increased movement of white blood cells. o Increased proliferation of white blood cells. o Enhanced rate of phagocytosis. However: o Most enzymes are optimised to work at 37C. o The cell membrane becomes much more fluid. o Proteins don’t fold properly. How membranes respond: Composition: o More saturated fatty acids. o More cholersterol. Heat shock proteins: o Proteins produced when a cell is exposed to increased temperature. o Increase in expression in response to other stresses (e.g., O2 deprivation, nutrient deprivation). o Main function is to help proteins fold properly so they can function properly. o Many copies as they are very important (redundancy). Robustness – extreme heat Geogemma barossii – archaea found found growing in a hydrothermal vent, can survive at 130C. Adaptations: High GC levels in third codon position = stronger bonding. Supercoiling DNA = harder to separate. Temperature stable proteins. Changes to membrane composition, including ether rather than ester bonds = stronger bonding between lipids. Robustness – low temperatures Problems: o Slow enzyme reactions. o Rigid and viscous membranes. o Ice crystals (can puncture holes in cell membranes). Glycoproteins = attached sugars function to stabilise the proteins structure in the extracellular environment and therefore offer some protection. o Antifreeze glycoproteins used in blood cells of antarctic fish stop/organise ice crystal formation Glycolipids = similar protective functions to protect from stress. Robustness – low oxygen Anoxia (no O2) --> hypoxia (low O2) --> normoxia (normal O2) --> hyeroxia (high O2). General hypoxia can occur: o Environmental O2 levels are low (e.g. high altitude). o Premature babies. o Poisoning. o Anaemia. Local hypoxia can occur because of: o Ischaemia = blood supply is cut off following heart attacks and strokes. o Cancer = tumour growth collapses blood vessels. Hypoxia inducible factors (HIFs) = oxygen sensing mechanisms that move to the nucleus and alter gene expresssion in response to hypoxia – normally degraded by the proteasome when oxygen is present. o Cell cycle stops (arrested at G1). o Switches to glycolysis and anaerobic metabolism to produce ATP. o Rapid down-regulation of protein synthesis. Angiogenesis = making new blood vessels, response to hypoxia as growth factors stumulate blood vessels to branch off, proliferate, and move towards the hypoxic cell. Robustness – nutrient deprivation Quiescence = state of reversible cell cycle arrest. Autophagy = cells form double-membraned vesiclse (autophagosomes) that sequester organelles/proteins/cytoplasm for delivery to the lysosome where they can be recycled to maintain nutrient and energy homeostasis. Proteasomes = multi-protein complexes that are able to degrade unwanted/damaged proteins to recycle amino acids for more protein synthesis. o Operate on one protein at a time for more precision. o Degrade proteins damaged by shock and deprivation. Robustness – toxic environments Toxic environments: o Radiation. o Free radicals (O2 molecule with unpaired electron = highly reactive). o Oxidative stress. o Toxins. o Poisons. Reative oxygen species: o O2 is the final electron acceptor in aerobic respiration, accepting 4 electrons, but sometimes this goes wrong and a highly reactive oxygen species is created. o Glutathione = major anti-oxidant that readily donates electrons to ROSs to form more stable molecules. o Superoxide dismutases = enzymes that convert highly reactive superoxide free radical (O2-_ to less reactive hydrogen peroxide (H202). o Catalase = then converts hydrogen peroxide (still a ROS) to water and oxygen. Robustness – repairing DNA damage DNA damage: Damage detected. Cell cycle stops. DNA repair is initiated. Too extensive = apoptosis. Unicellular life has a higher tolerance for DNA damage. Cancer = disease characterised by a loss of control over our own cells, happens when genetic damage occurs in cells that is not correctly repaired. Some mutations can change the way cells respond to signals, meaninf that these cells proliferate when they shouldn’t. ONE OF THE QUESTIONS How do heat shock proteins protect cells from high temperatures: a) Assist protein folding b) Decrease membrane fluidity c) Increase membrane cholesterol d) Reduce mitochondrial permeability e) Increase DNA supercoiling