Today, he answers the question:
How is the recent explosion of DNA sequencing technologies impacting the field of antibody engineering?
Dr. Crowe's Answer:
Well, I think we’ve all be watching the genomic sequencing effort with the human genome coming out and now every species on the earth is being sequenced. The technologies are very exciting because of the extreme throughput of nucleotide sequencing – either DNA or RNA – that can be achieved. Increasingly, these technologies are leaking into all biomedical disciplines.
I think in the last two or three years DNA sequencing has had an increasing impact on antibody engineering. The major impact is that most of the technologies in our field have focused on deriving single clones or single antibodies, monoclonal antibodies or sometimes building large libraries, but still selecting out individual members of those libraries. The amount of information that we get from such approaches is fairly limited. We end up with panels of antibodies that we study. But now with the sequencing technologies that are available, we can literally obtain millions or billions of sequences from a single sample. So, this opens opportunities to create or describe or analyze larger and larger libraries in humans or in experimental animals. So, I think that is the most exciting thing that the scale detail with which we can look at antibody repertoires now is just orders of magnitude more than was available to us previously.
One of the early impacts of not just the technologies – but in terms of the science and our understanding – is that the size of the repertoires and the complexity that we’re seeing is really changing our notion of how the human or animal B-cell response actually occurs. So, I think in the past – since we would obtain relatively few antibodies from our lab studies – we thought that the germinal center reactions that were responding to antigens generated a large number of variant antibodies. But in the end, one or a few B-cells won out based on affinity selection and the survivors from vaccination or an antigen stimulation were relatively limited. But now that we are looking at whole repertoires, we see that responses are not small collections of monoclonal antibodies, but that natural immune responses are really swarms of antibodies – large collections of variants that are highly related, but differ from each other by point mutations. Probably, there’s a wide spectrum of affinity represented in these swarms. Remarkably, they are maintained in a repertoire. There’s not the winnowing down or narrowing that we thought was occurring because of our previous limited techniques.
So, I think those are the biggest impacts. One is the explosive scale that we can use and also a new sense of a difference in the biology that we’re seeing from what we expected.
Download Dr.Crowe's full podcast here.
Dr. Crowe will be presenting Deep Sequencing the Human Antibody Response to Viral Infections and Human Germline Antibody Gene Segments Encode Polyspecific Antibodies. For more information on these sessions and the rest of the program, download the agenda. The Antibody Engineering & Therapeutics Event will take place December 8-12, 2013 in Huntington Beach, California. If you'd like to join us, as a reader of this blog,when you register to join us and mention priority code XD13172BLOGJP to save 20% off the standard rate.
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