Structure of an antibody. Image: Los Alamos National Laboratory.
A National Institutes of Health (NIH) grant to Los Alamos National
Laboratory Bioscience Division could help unravel the gnarly secrets of how
many human genes function.
Originally discovered in the Human Genome Project, the approximately 20,000
genes of the human body have been slow to reveal their exact roles. And one of
the best tools for exposing a gene’s function is to take the protein it
produces and generate specific antibodies, usually by vaccinating mice or
rabbits. Antibodies are specialized proteins the immune system deploys to block
the actions of potentially harmful bacteria and viruses.
By looking at antibodies, researchers can identify where, in a cell, genes
are active and under what conditions they increase or decrease their
expression. Antibodies are also one of the fastest growing classes of new
therapeutics, with sales of about $40 billion in 2010.
With the new NIH Common Fund grant of more than $4 million, researchers led
by Andrew Bradbury aim to develop an automated pipeline to generate antibodies
against human gene products, without using animals.
Instead Bradbury’s team will use “antibody libraries” expressed in
bacteria and bakers yeast. These libraries are enormous, comprising billions of
different antibodies, and the ultimate goal is to identify antibodies in the
libraries that recognize each human protein. The broad availability of
antibodies against all human proteins will facilitate the understanding of
human disease and provide likely targets for therapeutic intervention, with the
antibodies themselves potentially becoming therapeutic leads.
This project will leverage much of the technology that has been developed
over the years at LANL, including flow cytometry, antibody libraries, and
fluorescent protein technology, and has the potential to create a set of tools
applicable to many different problems of interest to sponsors beyond NIH,
including the U.S. Department of Energy and Department of Defense.