lecture 23 24/9

Introduction to Model Organisms

• Rationale for Model Organisms

  • Most molecular biology research avoids using humans as subjects for ethical and practical reasons.

  • Ethical Considerations: Cutting up babies or self-experimentation (e.g., DNA extraction from one's own hand) is unacceptable.

  • Practical Limitations of Humans as Model Organisms:

    • Difficulty in Maintenance: Humans are hard to keep in controlled environments for research. Similarly, choosing organisms like blue whales is impractical due to size and feeding requirements.

    • Reproduction Challenges: Many organisms are difficult to reproduce, or their reproductive cycles (e.g., parthenogenetic reproduction in single-sex species) do not model human sexual reproduction, which leads to a lack of genetic variation crucial for genetic studies.

    • Genetic Manipulation: Humans are not easy to genetically manipulate due to ethical concerns and technical complexity.

    • Biological Barriers: Some organisms (e.g., kelp) have biological components (e.g., polyglycocarbohydrate sludge) that prevent DNA sequencing with standard methods.

• Criteria for Selecting a Good Model Organism

  • Representativeness: Must model many biological processes and be representative of other organisms. It should not represent only a single, niche process.

  • Ready Availability: Should be easy to acquire, often found cohabiting with humans (e.g., in backyards).

  • Ease of Maintenance: Easy to keep alive, ideally in simple lab settings like test tubes or flasks, facilitating full reproductive cycles.

  • Easy and Quick Reproduction: Essential for genetic studies and generating sufficient experimental subjects. Pandas, for instance, are poor model organisms due to reproductive difficulties.

  • Abundant Information Available: Historically, species that have been domesticated or in close human vicinity for thousands of years often have a wealth of existing knowledge on their variability and phenotypes.

  • Sequenceable Genome: Crucial in modern biology to link traits to underlying genes.

• Exam Assessment Strategy

  • Emphasis will not be placed heavily on memorizing all model organisms, but understanding why they are used instead of humans is crucial.

  • Students should be able to recognize Latin species names and their corresponding uses, rather than needing to spell them perfectly.

  • Repeated exposure to these organisms throughout the course will aid recognition.

Prokaryotic Model Organisms

Escherichia coli (E. coli)

• Characteristics and Habitat:

  • Common pathogenic bacterium known for causing severe gastrointestinal issues (diarrhea, vomiting).

  • Naturally resides in the large intestine, where it plays beneficial roles if not misplaced.

  • Converts indigestible foods into essential vitamins (e.g., Vitamin K).

  • Aids in fiber breakdown and increases butyrate content in bowels; butyrates can fuel cells in a way that bypasses cancerous growth, suggesting healthy gut flora with E. coli can supplement cancer treatments.

  • "Always at an arm's reach" due to its presence in humans.

  • Numerous strains with various mutations are available.

• Biochemical Significance:

  • Possesses more catalytic enzymes than humans, despite being a single-celled prokaryote, because it must carry out all functions independently.

  • Carries many metabolic pathways on plasmids (smaller circles of DNA distinct from the main bacterial chromosome).

  • Horizontal Gene Transmission: Bacteria can swap these minor genomic elements even between different species, akin to collecting cards for advantageous traits (e.g., penicillin resistance, ability to metabolize plastic).

• Reporter Genes and Genetic Manipulation:

  • The model prokaryotic cell.

  • Easily made to "glow in the dark" using Green Fluorescent Protein (GFP) from the Aequorea victoria jellyfish.

  • GFP is a fluorescent protein, meaning it emits light in the visible spectrum (usually green) when exposed to specific wavelengths (e.g., black light), not bioluminescent like fireflies.

Mycoplasma genitalium (Minimal Model Organism)

• Characteristics and Parasitic Nature:

  • A parasitic organism, found as a penis rash (hence "genitalium").

  • Chosen as a "minimal organism" because parasites shed a considerable portion of their genome; the host provides essential resources (food, shelter), reducing the parasite's need for extensive metabolic machinery (e.g., fewer enzymes than E. coli).

• Synthetic Biology Breakthrough:

  • Scientists chemically synthesized its genome (580,000 nucleotides) by building individual nucleotides on a solid substrate using inorganic catalysts.

  • This synthetic DNA was then inserted into a different Mycoplasma species whose own genomic DNA had been irradiated and killed.

  • Result: A completely synthetic chemical chromosome capable of initiating a new life form—a functional, minimal organism, demonstrating the ability to create life from chemistry.

• Limitations in Understanding Life:

  • Despite its minimal nature and synthetic creation, about 30% of Mycoplasma genitalium's genes have unknown functions, yet removing them causes the organism to die.

  • This highlights a fundamental gap in our understanding of what constitutes basic life processes, even for the simplest known cell. Our knowledge often extends to "frills and whistles" (e.g., hair color, neurotransmitters) but not always the core mechanisms of cellular survival.

  • Building AI models based on this ignorance is unlikely to bridge these gaps.

Eukaryotic (Unicellular) Model Organisms

Saccharomyces cerevisiae (Baker's Yeast)

• Characteristics and Habitat:

  • Another single-celled organism, but unlike E. coli, it is a eukaryote.

  • Free-living yeast that ferments available sugars.

  • Found in nature on flowers (eating nectar) and rotting fruit.

  • Interest from home-brew communities in wild yeast strains for brewing.

• Advantages as a Eukaryotic Model:

  • Simplest eukaryote used for modeling biochemical processes that require membrane separation (e.g., transporters, channels, carriers, pumps), which are difficult to study in prokaryotes with only a single membrane.

  • Used by humans for thousands of years (e.g., beer making for 6,000-7,000 years, wine making potentially 9,000 years).

  • Has a reasonably simple genome.

• Genetic Manipulation and Applications:

  • Can be engineered to glow in the dark with GFP (e.g., glowing yeast at the bottom of beer).

  • Hypothetical glowing beer froth: A student proposed modifying a barley protein (serpent protein, responsible for foam) with GFP, requiring a PC2 license for genetic manipulation of barley.

  • It is the go-to cell for most eukaryotic needs until multicellularity becomes a requirement.

Multicellular Model Organisms

Chlamydomonas reinhardtii (Green Alga)

• Characteristics and Life Cycle:

  • Single-celled green alga, capable of movement via flagella (2 flagella, identical in structure to human sperm flagella).

  • Can reproduce both asexually and sexually, allowing for genetic analysis.

  • Habitat: Fresh water, soil.

  • Phototrophic: Uses light as its energy source via photosynthesis.

• Advantages as a Model Organism:

  • Studies of Flagellar Biology: Excellent for understanding cilia and flagella structure, function, and assembly, which are conserved across eukaryotes.

  • Photosynthesis Research: A simple eukaryotic model for studying photosynthesis mechanisms.

  • Cell Cycle and Development: Insights into cell division and the transition from single-celled to multicellular states.

  • Genetic Tractability: Easy to culture, short generation time, and well-developed genetic tools.

Caenorhabditis elegans (C. elegans - Nematode Worm)

• Characteristics and Biology:

  • A free-living, transparent nematode (roundworm), about 1 mm in length.

  • Eutelic: Possesses an invariant number of somatic cells (exactly 959 in the adult hermaphrodite).

  • Short life span (approx. 2-3 weeks).

  • Can be maintained in simple lab conditions (e.g., on agar plates feeding on E. coli).

• Advantages as a Model Organism:

  • Developmental Biology: Its transparent body and invariant cell lineage allow for direct observation of every cell division and differentiation event from zygote to adult.

  • Neuroscience: Simple nervous system (only 302 neurons), fully mapped connectome, allowing for detailed studies of neural circuits and behavior.

  • Genetics: Easily amenable to genetic manipulation; RNA interference (RNAi) is highly effective.

  • Apoptosis and Aging: Insights into programmed cell death and mechanisms of aging, many of which are conserved in humans.

Drosophila melanogaster (Fruit Fly)

• Characteristics and Biology:

  • Small insect, easy to culture in large numbers.

  • Short life cycle (approx. 10-14 days from egg to adult).

  • Well-characterized polytene chromosomes in salivary glands.

• Advantages as a Model Organism:

  • Genetics: A historic model for classical genetics; foundational discoveries in inheritance, mutation, and gene function.

  • Developmental Biology: Insights into body plan formation, organogenesis, and cell signaling pathways, many of which are conserved in vertebrates.

  • Neuroscience and Behavior: Studies on learning, memory, sleep, circadian rhythms, and neurological disorders.

  • Disease Modeling: Used to model human diseases such as Alzheimer's, Parkinson's, and various cancers.

Danio rerio (Zebrafish)

• Characteristics and Biology:

  • Small freshwater fish.

  • External fertilization and development.

  • Transparent embryos, allowing direct observation of internal organ development in live organisms.

• Advantages as a Model Organism:

  • Vertebrate System: Provides a vertebrate model for studying development and disease, more complex than invertebrates but simpler than mammals.

  • Developmental Biology: Excellent for observing embryogenesis, angiogenesis, and organ formation due to transparent embryos.

  • Genetics and Genomics: Easy to manipulate genetically; high-throughput drug screening capabilities.

  • Toxicology and Disease Modeling: Used to study environmental toxins and model human diseases affecting various organ systems (e.g., cardiovascular, neurological, hematopoietic).

Mus musculus (House Mouse)

• Characteristics and Biology:

  • Small rodent, widely used in research.

  • Mammalian physiology highly similar to humans.

  • Well-understood genetics and availability of numerous genetic strains and tools.

• Advantages as a Model Organism:

  • Human Disease Modeling: Best mammalian model for studying human diseases, drug efficacy, and toxicology due to close genetic and physiological homology.

  • Immunology: Crucial for understanding immune system function and disorders.

  • Genetics: Extensive resources for genetic manipulation (knockout, transgenic, CRISPR-Cas9 technologies); ability to study gene function in vivo.

  • Neuroscience: Used to investigate brain function, neurological disorders, and behavior.

Arabidopsis thaliana (Thale Cress)

• Characteristics and Biology:

  • Small flowering plant, member of the mustard family.

  • Fast life cycle (approx. 6 weeks from seed to seed).

  • Relatively small genome (approx. 125 Mb).

• Advantages as a Model Organism:

  • Plant Genetics and Development: The most widely used model for plant biology; insights into plant growth, development, reproduction, and response to environment.

  • Small Genome: First plant genome sequenced, making it easy for genetic and genomic studies.

  • Genetic Tractability: Easy to transform (introduce foreign DNA) and generate mutant lines.

  • Crop Improvement: Findings often applicable to understanding and improving crop species.