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Modelling Gene Regulation and Cellular Bioengineering

4.3 Modelling Gene Regulation Important Cellular Behaviours for Therapeutic Use · Cell interactions · Protein secretion · Migration · Control of cell identity · Proliferation Future Applications of Cellular Bioengineering · Designing cells with specific functionalities · Regenerative cells for transplantation · Novel food products Rational description of biological processes is required to · Make quantitative predictions · Understand governing parameters · Decompose complexity Central Dogma of Biology · DNA: Template of a long strand of nucleotides that store genetic information · Genes: Sequences of nucleotides · Transcription: Takes one single DNA strand, RNA acts as a messenger and creates a copy of that strand. · Translation: Ribosomes translate nucleotides in RNA template and create amino acids(building blocks on amino acids). . Proteins have different functions based on their structures · Transcription factors: Proteins that go back into the nucleus and start binding to DNA itself. Regulation of gene expression: Some proteins can regulate the transcription of genes · Transcription factors can go back to the DNA level and bond to DNA; they can initiate, increase/decrease the rate, or stop the transcription process(making a copy of DNA in the form of RNA). Oscillator circuit in bacterial cells · As the concentration of the protein increases, the fluorescent light becomes brighter. · As the concentration of the protein decreases, the fluorescent light becomes darker. Dynamics and Complex Behaviour of Network of Interacting Genes . Pause Impact: When the concentration of a gene increases until it reaches its maximum(due to a gene suppressor) and its concentration starts decaying. Biological example: Pulse response of gene to signal EGF, tells cells to proliferate · EGF stimulus: A protein that is added into culture media. Increase in concentration of growth factor(EGF stimulus). Cell Identity · Cell Types: Stem Cells, bone Cells, Blood Cells, Muscle Cells, Fat Cells, Skin Cells, Nerve Cells, Endothelial cells, sex cells, pancreatic cells, and cancer cells. . Phenotype of Cell: What tissue the cell belongs to How we measure cell identity · Cell identity(fate) on protein expression: using antibody followed by imaging . To find what cell types are in the colony, look for the different genes that exist in the system and tag each of those genes with different fluorescent colours. · This method is not efficient for large genes. · Method is precise Characterizing cell identity(RNA sequencing) . Quantifying reveals how much a gene exists in each of the cell towers · Pluripotent stem cells are at the very early stage of the embryo and are capable of differentiating to any cell type in the body. · IPSCs are induced pluripotent stem cells generated by reprogramming and offer huge potential for cell therapy. · Greater amount of stem cells = more cell renewal(self-replication/proliferation) = more differentiation of cells. Trafficking from trans-Golgi network and cell surface to lysosomes . Protein structure forms and can be transferred all the way to the plasma membrane and exterior of the cells. Cell-cell communication(Brain example) . Neuron needs to be activated to transmit this