Continuing our series of articles on Great British bioscience pioneers, we take a look at the career of Dr Marianne Brüggemann who has pioneered research on recombinant antibodies since the 1980s. She worked at the BBSRC-supported Babraham Institute from 1989-2010 where her work provided the platform technology behind the spin out company Crescendo Biologics, which has recently attracted a £19.5M investment.
How did your bioscience career first begin?
In 1984, after being awarded a Doctor of Natural Sciences by the University of Cologne, Germany, for my research at the Institute for Genetics, I worked as a postdoctoral scientist in the Department of Pathology, University of Cambridge. As an immunologist I was excited to learn molecular biology and used this as a tool to explore the immune system. I was very fortunate to obtain support from, initially, the DFG, a main German research funding organisation, then the Leukemia Society of America, followed by very generous MRC support to study human antibody expression.
What are you working on now?
I am the research director of Recombinant Antibody Technology Ltd. in Cambridge, affiliated with Open Monoclonal Technology Inc. in the US, focusing on human antibody expression in transgenic animals. Providing solutions to biological or technical problems and developing easily applicable new technologies is my driving force. A recent discovery was that large gene loci engineered in my laboratory could be expressed and diversified by the transgenic animal as efficiently as natural antibodies. My interests are antibody repertoires in all shapes and forms, from rays to rodents to camels.
What advances have you seen in your chosen field in the last 20 years?
I am still amazed at how many genes and interactions have been identified and how much there is still missing to fully understand immune function. Major technical advances concern molecular strategies and embryo or genome manipulations. There have also been major attitude changes, like focusing on research end points, possibly with commercialisation, and the replacement of animal research. Undoubtedly this will have a major impact concerning diagnostics and therapy options.
What are the five key bioscience milestones that you've been part of and when did these occur?
- 1989: first expression of human antibody repertoires in transgenic mice which resulted in a corner-stone patent. This was the result of a very productive collaboration with Michael Neuberger that continued for many years
- 1991: introduction of yeast artificial chromosomes into embryonic stem cells and derivation of mice expressing antibodies from a 1,300 kb translocus. A patent was granted
- 1998: first murine expression of a human Igl locus and first ~200 kb deletion of the mouse constant region locus, both with patents granted
- 2002: first heavy-chain-only antibodies expressed in mice, also with granted patent
- 2012: demonstrated that high affinity IgG antibodies develop naturally in Ig-knockout rats carrying the germline human IgH/Igk/Igl loci bearing the rat CH region. This new technology has been secured in several patents and the transgenic. rats are now being used by Genentech, Roche, Janssen, Pfizer, Merck KGaA, and Symphogen for the generation of human therapeutic antibodies
How has BBSRC supported you throughout your career?
The human antibody market, initiated by our 1989 joint patent, is now a billion dollar enterprise. A major part of this accomplishment is due to BBSRC and, previously, AFRC funding. Initially with Azim Surani, whose laboratory with Sheila Barton produced many transgenic mice for us, and then the newly established stem cell work, which was also generously supported by BBSRC. Later funding concerned locus manipulation in embryonic stem cells, derivation of manipulated mice and, most importantly, expression of heavy-chain antibodies, which will be another very lucrative antibody market.
When I took early retirement from the Babraham Institute in 2010, my patents, gene constructs and mice were sold to Crescendo Biologics – a spin out from the Institute that has attracted significant investment.