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Serge Muyldermans
Camel Heavy Chain Antibodies and Single-Domain Antibodies
VIB Department of Molecular and Cellular Interactions, Vrije Universiteit Brussel
PhD: Vrije Universiteit Brussel, Brussels, Belgium, '82
VIB Group leader since 1996 |
e-mail
phone +32 2 629 19 69
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Current team members
Group leader: Serge Muyldermans
Postdoctoral scientists: Cécile Vincke, Dirk Saerens, Nick Devoogdt
Ph.D. Students: Anne Kindt, Fang Zheng, Jochen Govaert, Trong Nguyen Duc
Support personnel: Nadia Abou
Keywords
camel heavy chain antibodies and single-domain antibodies - antibody engineering - phage display - high throughput screening - protein structure and conformation
Science
The occurrence of bona fide antibodies devoid of light chains in Camelidae was one of the major discoveries within our department. These so-called heavy-chain antibodies (HCAbs) bind antigen solely with one single variable domain, referred to as VHH. Methods were developed to clone the VHH repertoire of an immunised dromedary (or llama) in phage display vectors, and to select the antigen-specific VHHs from these ‘immune’ VHH libraries.
Our current research activities on camelid HCAbs and VHHs aims at three goals: (i) to increase the fundamental knowledge of VHH characteristics and HCAb ontogeny, (ii) to broaden the efficacy of VHHs and to extent their applications in medical or biotechnological fields where the unique VHH properties offer a clear advantage over other antibody formats, and (iii) to develop new VHH selection strategies that are amenable to a high throughput mode. The objective here is to arrive at a rapid identification of small molecular probes to be employed in biosensors, functional genomics, structural genomics and proteomics. Obviously, the appearance of HCAbs requires the acquisition of multiple events to allow their generation and maturation into functional molecules. The dromedary germline genes (V, D, and J) and constant immunoglobulin genes used to generate HCAbs were cloned. Analysis of these genes forms the cornerstone to understand the HCAb ontogeny in camelids, and might eventually lead to the generation of a Xeno-mouse producing camel HCAbs. The antigen-specific VHHs we retrieved have already excellent biophysical properties (antigen affinity, specificity, solubility, stability, small size, recognition of epitopes that are less immunogenic for conventional antibodies). We obtained the crystal structure of many VHHs in complex with their antigen, and this forms the basis for a further engineering of the VHHs to develop more versatile small molecular units. These small units are used as building blocks for more complex constructs, which are being tested as probe in biosensors, for tumour targeting, etc.
Selected Publications
Kirchhofer A, Helma J, Schmidthals K, Frauer C, Cui S, Karcher A, Pellis M, Muyldermans S, Casas-Delucchi C, Cardoso M, Leonhardt H, Hopfner K, Rothbauer U
Modulation of protein properties in living cells using nanobodies
NAT STRUCT MOL BIOL 17, 133-8, 2010
Rothbauer U, Zolghadr K, Muyldermans S, Schepers A, Cardoso M, Leonhardt H
A versatile nanotrap for biochemical and functional studies with fluorescent fusion proteins
MOL CELL PROTEOMICS 7, 282-9, 2008
Saerens D, Hassanzadeh Ghassabeh G, Muyldermans S
Single-domain antibodies as building blocks for novel therapeutics
CURR OPIN PHARMACOL 8, 600-8, 2008
Baral T, Magez S, Stijlemans B, Conrath K, Vanhollebeke B, Pays E, Muyldermans S, De Baetselier P
Experimental therapy of African trypanosomiasis with a nanobody-conjugated human trypanolytic factor
NAT MED 12, 580-4, 2006
Nguyen Viet K, Hamers R, Wyns L, Muyldermans S
Camel heavy-chain antibodies: diverse germline VHH and specific mechanisms enlarge the antigen-binding repertoire
EMBO J 19, 921- 930, 2000
Search Publications
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