Can you make use of an antibody that targets a human protein in another model organism? Under the right conditions, the answer is yes!
Non-human model organisms are a vital tool in the discovery of the fundamental principles of human genetics and molecular biology. The majority of commercially available antibodies, however, are designed to bind human or relevant mammalian models, limiting the ability to perform comparative and translational studies using non-human/non-mammalian animal model organisms.
What are Model Organisms?
Model organisms are non-human species that help scientists understand basic biological processes. They are morphologically well-characterized, easy to culture or keep in the laboratory, and ideally have a short generation time. They should be endowed with traits and behaviors that can be easily monitored and followed. In a perfect world they should additionally display a similar asset of genes as humans importantly large degree of sequence homology.
The conservation of disease pathways between model organisms and humans allows model organisms to be used to study disease pathogenesis and to develop drugs. Having said this, it should be emphasized that homologous (and different) molecular pathways may be employed to perform the same physiological task within relatively closely related mammalian species.
From higher vertebrates to microorganisms like bacteria and viruses, model organisms have become indispensable tools for fundamental biological and clinical research. They helped scientists both in identifying human disease gene homologues and aided in the characterization of their normal function and role in pathogenesis.
Over time there has been a major switch to more advanced biological model systems and functions, requiring the study of complex multicellular organisms.
Examples of Model Organisms used in Scientific Research
Figure 1. Comparison of four model organisms used in scientific research. Adapted from Wanyeon Kim et al., (2012)
Can You Use an Antibody Targeting a Human Protein in Another Model Organism?
The ability to use an antibody that is capable of recognizing a human protein in any non-human organism depends on the degree of homology between the two proteins.
This is possible due to the fact that most proteins (with few exceptions) share some degree of protein homology with other traditional or non-traditional model organisms even if they have split evolutionarily several hundreds of million years ago. Functional domains of proteins often show strong conservation due to their functional importance in ligand binding or catalytic activity.
As humans, we share about 99% of our genome with chimpanzees, 98.7% with bonobos, over 90% with the mouse and 75% with the fruit fly genome. Conserved sequences (orthologous and paralogous) that antibodies can recognize, are identical -or similar- sequences in DNA and RNA across species, sequences that might encode proteins with the same or a different function in different species.
The Protein Immunogen Sequence is the Key
Do you want to predict the immunohistochemical staining outcome in your model organisms? If you are able to align the immunogen sequence your antibody with the one in the species you want to test, you will achieve a first indication whether or not your immunohistochemical staining will work. An alignment score above 80% is a good indication, never an assurance, that the antibody may perform in your biological model.
The immunogen sequence determines the specificity of antibodies. It tells you information about which epitope the antibody will target. To compare the sequence alignment between two species, many of websites provide tools for calculating the percentage alignment, such as the Basic Local Alignment Search Tool (BLAST). Look at where the sequences match, and how similar the sequences are. The shorter the immunogen sequence the easier the antibody will cross-react with another species.
Some antibodies providers assist by listing all the necessary information on the product datasheet. Here is what you want to read on the antibody datasheet:
At Atlas Antibodies we provide the immunogen sequence for all our antibodies. This information helps you to assess whether the antibody may work in another model organism. Remember that if you test an antibody on a species that has not been validated yet, you are required to perform this validation yourself.
Figure 2 below is a typical example of such information from our catalog at Atlas Antibodies:
Figure 2. Essential information about the monoclonal antibody against Human Glial fibrillary Acidic Protein Anti-GFAP Antibody (AMAb91033)from Atlas Antibodies.
What if here is no Antibody Validated for My Species? Try Our Explorer Program
A better understanding of biology in various model organisms increases their value as a human translational research model, keeping them at the forefront of scientific research. In order to produce credible and reproducible results it is important to use antibodies that are validated for the specific species and application you are going to use.
However, as we all experience, the right antibody is sometimes impossible to find. This is why Atlas Antibodies, has developed the Explorer Program. With this initiative, we encourage you when suitable to use our antibody in your model, even if the antibody has not been verified for it and share the results with the scientific community and us.
This is how it works:
With your permission, we will share the results on the Researcher Contribution page on the antibody’s product page for others to see.
Dietrich MR. et al, (2014) Publication Trends in Model Organism Research. Genetics. 198(3): 787?794.
Wanyeon Kim et al., (2012) Model system in radiation Biology: Implication for Preclinical Study of Radiotherapy. Journal of Life Science Vol. 22(11):1558~1570
NHI-National Institute of General Medical Sciences: Using Research Organisms to Study Health and Disease.
Hunter P. (2008) The paradox of model organisms. EMBO reports. Vol. 9(8): 717