Nav: Home

Improving research with more effective antibodies

October 15, 2019

A new study points to the need for better antibody validation, and outlines a process that other labs can use to make sure the antibodies they work with function properly.

Antibodies are used in laboratories and clinics to study proteins, which are the biomolecules that translate information from an organism's genes into the structure, function, and regulation of its tissues and organs. Genetic mutations can cause protein imbalances or malfunctions, leading to human disease.

Antibodies allow scientists to study proteins by identifying where these proteins are in the cell and in what quantities. Because of their importance, many companies make antibodies as commercial products, which they sell for scientific studies and for use in clinical settings.

Previous studies, however, have shown that many commercially available antibodies do not specifically identify the proteins they are supposed to detect. This calls into question research that has used these antibodies, and underlines the need for an accurate, standard process to test the quality of antibodies.

A team led by Peter McPherson at The Neuro (Montreal Neurological Institute and Hospital) decided to use a human protein as a test case, both to highlight the antibody validation problem and to demonstrate a procedure that other labs can use to validate their antibodies.

They focused on the protein product of a gene, C9ORF72, mutations in which are the major genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia.

After testing 16 antibodies advertised by companies as specific for C9ORF72, the team found that only one of the 16 accurately detected C9ORF72 in immunofluorescence, a technique in which antibodies stain proteins so they can be seen under a microscope. Other techniques were successful with only two other antibodies. The antibodies that passed the validation criteria have not yet been used in scientific studies. Antibodies that failed the validation criteria have been used in multiple studies.

The results call into question previous studies that used antibodies to detect C9ORF72 that either do not recognize the protein at all or recognize additional, unrelated proteins. Moreover, they emphasize the need for better antibody validation.

Science is facing a crisis in reproducibility; study results are often impossible to replicate. In cell biology, lack of effective antibodies contributes to the problem. In their paper, published in the open access journal eLife on Oct. 15, 2019, the researchers describe their method of validation, which other labs can replicate to make sure their antibodies function properly.

"As we worked on our C9ORF72 paper, it became less about one gene and more about a template other labs can use to validate antibodies," says McPherson. "The procedures we use are not revolutionary, and in fact this makes our approach widely applicable to any laboratory skilled in the art, yet to my knowledge this is one of the first papers to describe a streamlined process for antibody validation. A large part of the reproducibility crisis is because of poor antibody validation. We owe it to funders and patients to do better."
-end-
This work was supported by a grant from the Motor Neurone Disease Association (UK), The ALS Association (USA), The ALS Society of Canada and by an ALS Canada-Brain Canada Arthur J. Hudson Translational Team Grant. It was completed as part of the ALS-Reproducible Antibody Platform, a project designed to test antibodies against the protein products of ALS disease genes.

The Neuro

The Neuro - The Montreal Neurological Institute and Hospital - is a world-leading destination for brain research and advanced patient care. Since its founding in 1934 by renowned neurosurgeon Dr. Wilder Penfield, The Neuro has grown to be the largest specialized neuroscience research and clinical center in Canada, and one of the largest in the world. The seamless integration of research, patient care, and training of the world's top minds make The Neuro uniquely positioned to have a significant impact on the understanding and treatment of nervous system disorders. In 2016, The Neuro became the first institute in the world to fully embrace the Open Science philosophy, creating the Tanenbaum Open Science Institute. The Montreal Neurological Institute is a McGill University research and teaching institute. The Montreal Neurological Hospital is part of the Neuroscience Mission of the McGill University Health Centre. For more information, please visit http://www.theneuro.ca

McGill University

Related Antibodies Articles:

Improving research with more effective antibodies
A new study points to the need for better antibody validation, and outlines a process that other labs can use to make sure the antibodies they work with function properly.
How to enable light to switch on and off therapeutic antibodies
IBS researchers have developed a new biological tool that activates antibody fragments via a blue light.
Ebola antibodies at work
Scientists in Israel and Germany show, on the molecular level, how an experimental vaccine offers long-term protection against the disease.
How new loops in DNA packaging help us make diverse antibodies
It's long been known that our immune cells mix and match bits of genetic code to make new kinds of antibodies to fight newly encountered threats.
Immunological discovery opens new possibilities for using antibodies
Researchers from the University of Turku have discovered a new route that transports subcutaneously administered antibodies into lymph nodes in just a few seconds.
Rheumatoid arthritic pain could be caused by antibodies
Antibodies that exist in the joints before the onset of rheumatoid arthritis can cause pain even in the absence of arthritis, researchers from Karolinska Institutet in Sweden report.
Humanization of antibodies targeting human herpesvirus 6B
A Japanese research group have succeeded in humanization of mouse antibodies that can neutralize the infection caused by human herpesvirus 6B.
Edible antibodies to treat and prevent gastrointestinal disorders
Therapeutic antibodies are increasingly being used in the clinic for the treatment of various diseases.
Antibodies stabilize plaque in arteries
Researchers at Karolinska Institutet in Sweden have found that type IgG antibodies play an unexpected role in atherosclerosis.
Protective antibodies also found in premature babies
Even premature babies carry anti-viral antibodies transferred from the mother, researchers at Karolinska Institutet in Sweden report in a paper on maternal antibodies in newborns, published in the journal Nature Medicine.
More Antibodies News and Antibodies Current Events

Top Science Podcasts

We have hand picked the top science podcasts of 2019.
Now Playing: TED Radio Hour

Risk
Why do we revere risk-takers, even when their actions terrify us? Why are some better at taking risks than others? This hour, TED speakers explore the alluring, dangerous, and calculated sides of risk. Guests include professional rock climber Alex Honnold, economist Mariana Mazzucato, psychology researcher Kashfia Rahman, structural engineer and bridge designer Ian Firth, and risk intelligence expert Dylan Evans.
Now Playing: Science for the People

#541 Wayfinding
These days when we want to know where we are or how to get where we want to go, most of us will pull out a smart phone with a built-in GPS and map app. Some of us old timers might still use an old school paper map from time to time. But we didn't always used to lean so heavily on maps and technology, and in some remote places of the world some people still navigate and wayfind their way without the aid of these tools... and in some cases do better without them. This week, host Rachelle Saunders...
Now Playing: Radiolab

Dolly Parton's America: Neon Moss
Today on Radiolab, we're bringing you the fourth episode of Jad's special series, Dolly Parton's America. In this episode, Jad goes back up the mountain to visit Dolly's actual Tennessee mountain home, where she tells stories about her first trips out of the holler. Back on the mountaintop, standing under the rain by the Little Pigeon River, the trip triggers memories of Jad's first visit to his father's childhood home, and opens the gateway to dizzying stories of music and migration. Support Radiolab today at Radiolab.org/donate.