(2) From the Origins of Cells to Synthetic Cells
What is life?
Self assembly of parts, growth, replication, catalysis, emerging properties, fidelity of process (robustness)
Origin of Living Cells
1. 2,000,000,000 years ago a primitive cell developed internal membranes to become the ancestral eukaryote – able to engulf other organisms.
2. It incorporated a respiratory prokaryote (aerobic heterotrophic prokaryote) which evolved into the mitochondrion to produce the ancestral heterotrophic eukaryote (The mitochondrial ancestor identified: John & Whatley Nature 254, 495).
3. Some of the mitochondria-containing eukaryotes took up another prokaryote (a photosynthetic organism resembling present day cyanobacteria chloroplast) ancestral photosynthetic eukaryote
how do plants and animal cells differ?
Plants only: chloroplasts, central vacuole and tonoplast, cell wall, plasmodesmata
Animals only: lysosomes, centrioles(plants other than flowering and conifers), flagella (in some plant sperm) synthetic biology
creating synthetic cells
Cell signalling
Purpose
Responding and adapting, mostly involving the exchange of chemical signals
Prokaryotes: environmental changes, temperature, osmotic stress, nutrients control movement toward/away from the stimulus (flagella) or synthesis of new proteins
Unicellular organisms talk about sex i.e. yeast
Multicellular respond to growth factors, hormones…
How signals are receieved and processed (transduced)
Signal transduction: method of cell’s response, studied to understand cells and treat disease (cancer) on:
Yeast, Nematode worms, Fruit flies, Rodent cell culture models/mouse genetics, Human cell culture models
Ligands – first messenger/external signal/stimuli i.e. proteins, peptides, lipids, small molecules
Receptors – specific cellular proteins (membrane spanning) ligand ‘switches’ receptor on
Ion channel-linked receptors
G-protein-linked receptors
Enzyme-linked receptors (protein kinases)
Transduction – converts/amplifies initial stimuli to internal/2nd messenger
Receptor recruits effectors (enzymes) that propagate (transduce) the signal further into the cell/catalyse the formation of second messenger molecules i.e. relay proteins
Amplification
each receptor activates many transducers/opens ion channel/enzymatic generation (many molecules created at each step)
Response – response proteins activation of metabolic enzymes/rearrange cytoskeleton/ transcription factor leading to change in gene expression i.e. Ras-MAP kinase pathway can have many responses
Stem cells
Totipotent any cell type Pluripotent major lineage (ectoderm, nerve) Multipotent tissue
Self renewal: one stem and one terminally differentiated
Human Development: Blastocyst inner pluripotent cells endoderm/mesoderm/ectoderm gastrula
Adult:
Constant turnover:
Haematopoietic system – bone marrow
Hair follicle - bulge
Interfollicular epidermis – basal layer epidermis
Low/no turnover
Brain – subventricular/subgranular zone
Skeletal muscle - basement membrane & muscle fibres
How they’re Triggered
Genetic Factors: Transcription factors turning on genes/ repressors inhibiting transcription
Epigenetic factors: chromatin remodeling (tight packing), methylation of DNA (silences)
Triggers: chemical signals, retinoic acid
Stem cell niches: growth factors, extracellular matrix/physical properties, skeletal muscle & satellite cells, hair follicles and bulge, neurogenesis at olfactory bulb and central part of hippocampus
Induced Pluripotent stem cells
De-differentiation for regeneration in amphibians and worms
Cancer cells acquire stem cell like properties
Nobel prize 2012, induced using MyC and Klf2 – nucleus of frog egg replaced with tadpole
Transport into and around the cell
Composition of Membrane fluid mosaic model; 50 lipids: 1 protein – evidence by surface tension lipids; vary dependent on head group, chain length,