Systems biology Flashcards
True or false: genotype can refer to only one gene
True
- Genotype can refer to only one gene, or all the genes in a genome
- Genotype: gene(s) inherited by an organism
What are the two things that result in phenotypic variation (what makes individuals different from each other?)
- Different alleles (slight variation in gene sequence results in changes in amino acid sequence of proteins.
- Differential regulation of gene and protein expression (deep blue eyes vs. light blue eyes)
Why do identical twins have slight differences in phenotypes?
Due to epigenetics
- Chromatin packing, nothing to do with nucleotide sequence
- More histones (packed chromatin)= gene silencing and vice versa
Every cell in an organism has an identical genome (DNA sequence). How do different cell types exist?
Due to regulation of which genes are being turned on and off
If we can control tissue-specific transcription, then it is possible for transdifferentiation (changing one tissue into another type of tissue). What are some applications of this?
Regenerative medicine (e.g. making skin grafts for burn victims)
True or false: Macromolecules work individually in a cell to carry out cellular processes
False. Cellular processes involve the concerted action of macromolecules.
If a protein was missing in a ribosome complex (or any protein complex), would the complex remain functional?
Probably not, every protein is usually required in a complex (because these macromolecules are dependent on each other).
How do extracellular stimuli/hormones communicate to genes?
By signal transduction pathways.
What do the the signal transduction pathway components include?
Ligand, cell surface receptor, kinase cascade, transcriptional regulator
What do signal transduction cascades ensure?
Proper gene expression or physiological response from stimulus.
What 4 things are needed to fully decipher and understand how life works?
- Identify all the parts/macromolecules in the cell/organism (nucleic acids, proteins, lipid, metabolites)
- Measure the abundance and dynamics of each macromolecule
- Determine the regulation (multiple levels) and function of each macromolecule (i.e. how does a cell know when to turn a gene on and off?)
- Determine interactions between macromolecules and their biological significance.
Why do we sequence genomes?
To understand how the types and abundance of RNA and proteins result in a phenotype of an organism.
What is systems biology?
The study of an organism (or cell), viewed as an integrated and interacting network of genes, proteins and biochemical reactions which give rise to life.
Describe the systems biology approach
The approach is to analyze all the components (e.g. genes, mRNA and proteins) and their interactions at once to obtain a systems view of a cell/organism (opposite of reductionism)
What is reductionism?
When scientists study one or two components (e.g. their favourite genes)
What was the systems biology field driven by?
This recent field of science was driven by the human genome sequence project and the development of high-throughput technologies to monitor global levels of molecules and interactions simultaneously in a cell.
What are some potential benefits of a system understanding of a cell/organism?
Health, agriculture, ecology, environment.
What four components are needed for a system-level understanding?
- Systems Structures
- System Dynamics
- System Control
- System Design
Describe the systems structures component
What is the parts list?
- Macromolecules: Genes, RNA, proteins, lipids, metabolites
- Macromolecular interactions (e.g. transcriptional regulation, protein binding and biochemical activity)
What are network structures made of? (2)
Nodes (genes, proteins, etc) and edges (binding and regulatory interactions)
The edges of protein-protein interactions (show/do not show) directionality
Do not show
The edges of gene regulatory interactions like a transcription factor binding a gene (show/do not show) directionality
Show
How is the connectivity of network structures defined?
The number of interactions between nodes.
Does a mutation on a transcription factor with higher or lower connectivity have a greater effect on a cell?
Higher connectivity
In networks of signal transduction pathways, arrows show…
An activating interaction
In networks of signal transduction pathways, “T”s show…
A repressing interaction
What is the most extensively studied eukaryotic organism?
Saccharomyces cerevisiae
Describe the system dynamics component
How do the biological networks change over time during development or to various environmental conditions?
As cells differentiate (example of system dynamics), what three parameters of mRNA/proteins change in the cell?
- Abundance (synthesis and degradation)
- Interactions (complex components, what are the enzymes being turned on and what proteins are interacting?)
- Activity (enzymes)
What does detecting the changes in mRNA/protein abundance, interactions and activity allow for in terms of gene function?
Detecting these changes allows inference of gene function.
Describe the systems control component
What control mechanisms exist to keep the cell fairly robust to perturbations (genetic mutations/environmental insult) to minimize malfunctions?
What are the four components of systems control?
- Negative-feedback and feed-forward control
- Redundancy/backup (cells have backup systems incase something happens to specific genes)
- Structural stability: chaperones, DNA repair and checkpoints
- Modularity: sub networks are physically or functionally insulated so that failure of a component will not result in catastrophe
Describe the “and” component of feed-forward control
If both indirect (through B) and direct activation of C is needed, then activation can be delayed (because it takes longer)
Describe the “or” component of feed-forward control
Protection from transient inactivation
- If something happens to B, A can still activate C -> can compensate for the loss of a component in a pathway.
Describe the systems design component
Can we rewire the network to cause a desired phenotype?
What is meant by “rewire” in the systems design component?
Perturbation of specific gene activity predicted by systems theory rather than trial and error to change global gene expression
What is an example of the systems design component concerning embryonic stem cells?
Overexpression of 3-4 transcription factors simultaneously to change somatic cells into an embryonic stem cell
What is differentiation therapy in cancer treatment?
Inducing the reversion of malignancy with the restoration of mature cells of the same lineage.
- Used to reprogram cancer cells to differentiate into a more benign state with the approach of systems design.
True or false: the systems biology approach only concerns the wet lab
False
- The systems biology approach involves a continuous interplay between experimental discoveries (wet lab) and hypothesis-driven model simulations/predictions (dry lab)
What are the 4 steps in systems biology when trying to produce a predictive model?
- Define all components in the system and model based on pre-existing genetic and biochemical knowledge
- Systematically perturb and monitor components of the system (test to see if the model is accurate using things like CRISPR)
- Reconcile the experimentally observed responses with those predicted by the model (the models get better and more accurate)
- Design and perform new perturbations experiments to distinguish between multiple competing models.
After identifying all the genes, we need to determine the function of every gene in the genome in order to decode how life works.
What are the four main approaches/assays used to determine the function of genes?
- Perturb gene function and study phenotype (knockouts)
- Measure mRNA expression in various cells
- Measure protein abundance, cellular localization and protein-protein interactions
- Predict and elucidate structure of protein from gene and amino acid sequences (looking at the raw DNA and amino acid sequences)
What is the general approach used to determine the function of every gene in the genome? What are “omics”?
High-throughput “omics” technologies to functionally characterize all the genes in the genome in a single experiment.
- Omics aims at the collective characterization and quantification of pools of biological molecules that translate into the structure, function, and dynamics of an organism or organisms.
Describe reverse genetics
Delete every gene and study the phenotype to determine the function of each gene
Describe genetic interaction mapping
Create all double mutant combinations and assay for lethality
- Can take a mutant gene and delete every other gene separately, and then see which combinations lead to lethality.
- Good for finding drug therapies
Describe proteomics/interactomics
Determine abundance and interactions of all proteins using 2-hybrid/mass spectrometry
Describe metablomics
Determine abundance of metabolites using mass spectrometry and NMR
Describe transcriptomics
Determine abundance of all RNA molecules (DNA microarrays/RNA-Seq)
What does gene expression refer to? What does protein expression refer to?
Gene expression: “turning on” a gene to produce RNA and protein (coding gene)
Protein expression: The type and abundance of proteins in the cell.
