Bio Lab Research - Genetics, Animal Models

By pjain      Published Feb. 13, 2021, 1:48 a.m. in blog Health   

Lab Research 101

Lab Studies Overview

Cellular Studies - In Vitro, In vivo

Toxicity Liver Cell Reaction Studies

Simulation

Increasingly, some technical alternatives, such as computing models that use artificial intelligence and machine learning systems. They can calculate what may happen if you put a medicinal compound in a body.

But you can't avoid testing medicines on animals, including humans, in the end. How else would you know whether there are any benefits for human life?

Animal Studies

Human Trials to Side-effects

Even further down the track, in human clinical trials, people can have extreme and adverse reactions to a drug in development. And that's when the drug has been somewhat refined to limit negative outcomes.

Efficacy Studies - Is it really Better?

Symptom relief vs Evidence-driven Outcomes studies

Large Scale DIVERSIFIED Human Trials to validate demographics and Side-effects

Evolution, Genetics keys and Translational Research

Ethics in Lab Research

Ethics in Industrial Testing - Cosmetics

Ethics in research

Vaccines and other medicines are tested on non-human animals to look for dangerous side-effects long before they get tested on people. The animals never sign "consent forms" and often are destroyed in "destructive testing" i.e. dissection, and there is little reuse once an experiment is complete as scientists want to start from a blank slate.

  • Ethics can be complex?
  • Is it okay to just go ahead and test potentially lethal chemicals?
  • What about psychological trials, like studying pain stimuli on mice? Is that okay?

  • What is relative value?

  • Lets say 10,000 monkeys are killed during drug development that can save 1000s of human lives?
  • Does that mean that a monkey's life is worth less than a human life?

Regulations

There are regulations to ensure the welfare of animals in research. Increasingly, some technical alternatives that can accelerate drug discovery and reduce animal cruelty, such as computing models that use artificial intelligence and machine learning systems.

  • https://grants.nih.gov/grants/policy/air/NIH_ensure_welfare.htm

Guidelines for ethical Animal Models

Human Experimentation

Aging Studies eg Regenerative Animals

Animal Models

Overview, Animal Model References

Model organisms — or research organisms, as they are also known — are living things that scientists, such as biologists, use to study human and other animal or plant life. Usually lab movies depict mainly monkeys and mice and they ARE incredibly important for the study of human disease and ageing, because they are genetically so similar to humans and it has led to some major scientific breakthroughs.

But there are far more models - from single-celled bacteria to viruses and fungi, to more complex organisms like frogs and a salamander called axolotl.

--- Vertebrate animals

Vertebrates are animals with a spine.

However, Vertebrates like Zebrafish have two eyes, a mouth, a brain, intestine, pancreas, liver, bile ducts, kidney, a heart, ears, nose, cartilage, and teeth… just like humans.

Zebra Fish - 70% Genetic to Humans

Zebrafish, Danio rerio a freshwater tropical specimen

  • 70% of their genes are similar to human genes.

Benefit: they are virtually transparent offering scientists with an rare view of an animal's internal anatomy. Can come in handy in studying response to , Toxicity. Uses: Cancer, neurocognitive research like Alzheimer's, Congenital heart disease

Frogs

Xenopus Laevis is a common lab frog from 1000s of species.

Benefits are large embryos and transparent during development.

Frogs are very sensitive to environmental chemicals and can be used for toxicity studies.

Research areas include pregnancy, stem cell research and cloning

Axolotl

Use: Regeneration of limbs and organs - role in study of genetics and aging Problem: Critically Endangered in wild - used as pets but going extinct outside labs.

Rodents : Rats and Mice Experimental Dominate

As rodents, rats are surprisingly similar to primates, but far more convenient due to rapid breeding rates, smaller size. In a facility you can literally study thousands of mice and rats.

--- Mammals

Mice

Mice bear the brunt of the Lab load - as they are highly compatible with Humans

Scientists recently reported that they had cured mice of paralysis after the animals had suffered a spinal cord injury.

Knockout Experimental Mice are Critical

Rats - Bigger Organs

Naked Mole Rats - Long Life

--- Primates Experimentation

  1. Ethically, monkeys are used in animal research only if a particular phenomenon cannot be studied on any other species of animal, such as mice, fish or fruit flies. They are used primarily for the final drug safety tests on new medicines before they are used on humans." - Max Planck Society guidelines

  2. The RSPCA, an animal welfare charity in the UK, says primates are "highly intelligent animals […] that suffer in similar ways to us." It goes on to say that "the capture of wild primates for use in breeding colonies and for experiments in some countries causes very significant suffering — we believe this is completely unacceptable."I

Rhesus Macaque

Macaques are already among the most commonly used non-human primates in biomedical research.

  • A small size is the dominant primate model
  • Used to study esp. in near pre-human clinical trials for Drug safety testing
    • Infectious disease
    • Vaccine

Cynomolgus macaque monkeys

Also known as long-tailed or crab-eating macaques may be the focus of a "new era of animal models for Dementia, autism and other brain and psychiatric diseases.

Larger Mammals - Experimentation

Horses for Serum

Elephants

Insects, Worms, Fish, Amphibians

Fruit Flies - 75% genetic similarity (disease)

Drosophila melanogaster

  • Share 75% of our disease causing genes eg Metabolic

  • Short life benefits rapid turnover of drug testing

  • Often used in drug testing for nervous system
  • Sexual studies and selection

--- Invertebrates

Invertebrates have no spine. They can live on land or in water.

Hydra - Aging research

Hydra Vulgaris

  • An aquatic animal
  • It is "immortal" due to its regenerative skills, and it doesn't deteriorate with age
  • Reproduces asexually - only one parent, all children are exact clones!

Nematode

Also called Round Worm C. Elegans, it is an invertebrate animal that is self-fertile ie can fertilize itself with both male and female organs.

Benefit: Transport body - easy to manipulate cells, and see results Uses: Genetics, development and physiological studies

Jellyfish - Long Lived

Plant Studies and Unicellular

Viruses - study to CRISPR vectors!

  • Viruses are "simple" in just being a protein/membrane shell around a RNA. It is a parasite and uses host cellular machinery to reproduce and spread.
  • Benefits - rapid reproduction rates
  • Uses: Gene structure, gene regulation, Vaccine development, anti-viral

  • Lambda phage is a temperate virus, which infects host bacteria, such as E.coli.

  • was used to develop RNA sequencing

  • T4 phages

  • Tobacco Mosaic virus

Prokaryote Bacteria

Prokaryotes are more complex than viruses but still lacks a distinct nucleus, the thing that controls the activity of a cell.

Benefits: Grow fast and cheap Products: Many biochemistry products are produced by Bacteria

  • E.coli (Escherichia coli)
  • Thrives with and without oxygen
  • Very common in our environment

Eukaryotes

Eukaryotes have a clearly defined nucleus and evolved about 2 billion years ago.

They include protists. Protists are often but not exclusively microscopic, single-celled organisms.

  • Being nuclei based cells they are much closer to human cells
  • Benefit is easy to manipulate

Baker's Yeast - 25% genetic similarity

  • 25% same genes as humans!
  • Baker's yeast is used in genetic research

Fungi

Eukaryotes also include fungi. There's Neurospora crassa, an orange bread mold, for instance, that's been used to study metabolic regulation and the circadian rhythm — the latter being a field that won a Nobel Prize only a few years ago.

Fungi are used in genetic research esp. Coprinus cinereus mushrooms. They have been useful in the study of meiosis, or cell-division, which is important for understanding reproduction.

Mustard family - Thale Cress

Arabidopsis thaliana is also a eukaryote. It belongs to a group of so-called higher plants.

  • Benefits are in its small small and easy to grow
  • it has a short generation time : the average time from the birth of one living thing to the birth of its offspring
  • It produces up to 10,000 seeds per plant (tiny mustard seeds)
  • It's easy to manipulate and mutate via pollination
  • It has since become integral to genetics studies and stem cell research and is still delivering insights.

  • 1821 has been used for 200+ years since a Swiss botanist called A.P. de Candolle coined the term Arabidopsis to describe a group of Brassicaceae plants in the mustard family in 1821.

  • Later a German botanist, Friedrich Laibach, then "established the mustard plant A. thaliana (L.) Heynh as a model organism in plant genetics.
  • It was the first plant to have its complete genome sequenced.

Tomatoes, Peas

  • Easy to grow in green houses, they are often both used for plant and agricultural studies, as well as genetics fundamentals.

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