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Per Åke Nygren, PhD
Professor in Molecular Biotechnology
Contact Info
Department of Molecular Biotechnology
School of Biotechnology, AlbaNova University Center
KTH Royal Institute of Technology
SE-106 91 Stockholm, Sweden
Phone: +46-8-5537 8328
Fax: +46-8-5537 8481
Email:
Web:http://www.biotech.kth.se
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Short Biography |
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| Per-Åke Nygren received his PhD in 1992 at the Royal
Institute of Technology, Stockholm on the characterization
of a serum albumin binding receptin protein of bacterial
origin. He has since then acted as group leader and was
appointed professor in Molecular Biotechnology in 1999.
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| The research was primarily focused on the use of affinity
gene fusion strategies to facilitate recombinant protein
production, purification and immobilization. In collaboration
with researchers at Karolinska Institutet, a gene fusion-based
concept for increasing the serum half-life of recombinant
protein in vivo was devised in the early 1990s, utilizing
a serum albumin binding fusion partner. The research group
early started using the power of protein library technology
to solve complicated biological questions related to enzyme
engineering, aqueous two-phase partitioning, gene expression
and biorecognition. The major focus under later years has
been in the field of scaffold engineering. The research
group was one of the groups pioneering the development of
novel affinity reagents based on other frameworks than the
immunoglobulin fold. Using libraries of a small (58 aa),
non-cysteine, three-helix bundle protein as framework, so
called Affibody binding proteins have been developed and
used for variety of applications. These efforts have been
associated with an interest also for development of new
methodologies for library handling and selection. |
| Per-Åke Nygren is presently the Vice Director for
the VINN Excellence Centre "AlbaNova VINN Excellence
Centre for Protein Technology (ProNova)" (www.biotech.kth.se/pronova),
co-cordinator for "Alternative Binders" in the
FP6 EU network "ProteomeBinders" (www.proteomebinders.org),
and one of the PIs within the newly started FP7 EU collaborative
project "FLUODIAMON" (cancer diagnostics). He
is also the Head for the Department of Molecular Biotechnology,
KTH and Director for post-graduate studies at KTH School
of Bíotechnology. He has supervised or co-supervised
some 20 research students to their doctoral or licentiate
degrees. |
| Some selected publications |
| • |
Hammarberg, B., Nygren,
P.-Å., Holmgren, E., Elmblad, A., Tally,
M., Hellman, U., Moks, T. and Uhlén, M. [1989] “Dual
affinity fusion approach and its use to express recombinant
human insulin-like growth factor II” Proc. Natl.
Acad. Sci. USA. 86, 4367-4371. |
| • |
Nygren, P.-Å., Flodby,
P., Andersson, R., Wigzell, H. and Uhlén, M. [1991]
“In vivo stabilization of a human recombinant
CD4 derivative by fusion to a serum-albumin-binding receptor”
Vaccines 91, Cold Spring Harbor Laboratory. 363-368.
(Peer reviewed Conference proceeding; US patent 6267964;
EPO patent 0486525) |
| • |
Nilsson, P., Persson, B., Uhlén, M.
and Nygren, P.-Å. (1995) "Real-time
monitoring of DNA manipulations using biosensor technology"
Anal. Biochem. 24, 400-408. |
| • |
Nord, K., Nilsson, J., Nilsson, B., Uhlén,
M and Nygren, P.-Å. (1995) "A
combinatorial library of an α-helical bacterial receptor
domain" Protein Engineering 8, 601-608. |
| • |
Nord, K., Gunneriusson, E., Ringdahl, J.,
Ståhl, S., Uhlén, M. and Nygren, P.-Å.
(1997) "Binding proteins selected from libraries of
an α-helical bacterial receptor domain" Nature
Biotechnology 15, 772-777. |
| • |
Jansson, B., Uhlén, M. and Nygren,
P.-Å. (1998) "All individual domains
of staphylococcal protein A show Fab binding" FEMS
Immunol. Med. Microbiol. 20, 69-78. |
| • |
Gunneriusson, E., Nord, K., Uhlén,
M. and Nygren, P.-Å. (1999) "Affinity
maturation of a Taq DNA polymerase specific affibody by
helix shuffling" Protein Engineering 12, 873-878. |
| • |
Legendre, D., Laraki, N., Gräslund,
T., Björnvad, M. E., Bouchet, M., Nygren, P.-Å.,
Borchert, T. V. and Fastrez, J. (2000) “Display of
active subtilisin 309 on phage: Analysis of parameters influencing
the selection of subtilisin variants with changed substrate
specificity from libraries using phosphonylating inhibitors”
J. Mol. Biol. 296, 87-102. |
| • |
Nord, K., Gunneriusson, E., Uhlén,
M. and Nygren, P.-Å. (2000) "Ligands
selected from combinatorial libraries of protein a for use
in affinity capture of apolipoprotein A-1 and Taq
DNA polymerase" J. Biotechnol. 80, 45-54. |
| • |
Lehtiö, J., Teeri, T. and Nygren,
P.-Å. (2000) "Alpha-amylase inhibitors
selected from a combinatorial library of a cellulose binding
domain scaffold" Proteins: Struct. Funct. Gen.
41, 316-322 |
| • |
Danielsen S., Eklund, M., Deussen, H.-J.,
Gräslund, T., Nygren, P.-Å.
and Borchert, T. [2001] "In vitro selection of enzymatically
active lipase variants from phage libraries using a mechanism-based
inhibitor" Gene 272, 267-274. |
| • |
Karlström, A. and Nygren, P.-Å.
[2001] "Dual labeling of a binding protein allows for
specific fluorescence detection of native protein"
J. Anal. Biochem. 295, 22-30. |
| • |
Nord, K., Nord, O., Uhlén, M., Kelley,
B., Ljungqvist, C. and Nygren, P.-Å.
(2001) “Recombinant human factor VIII-specific affinity
ligands selected from phage-displayed combinatorial libraries
of protein A" Eur. J. Biochem. 268, 4269-4277. |
| • |
Bandmann, N., Van Alstine, J., Veide, A.
and Nygren, P.-Å. (2002) "Functional
selection of phage displayed peptides for improved aqueous
two phase partitioning of recombinant proteins" J.
Biotechnology 93, 1-14. |
| • |
Rönnmark, J., Hansson, M., Nguyen, T.,
Uhlén, M., Robert, A., Ståhl, S. and Nygren,
P.-Å. (2002) "Construction and characterization
of affibody-Fc chimeras produced in Escherichia coli"
J. Immunol. Meth. 261, 199-211. |
| • |
Eklund, M., Axelsson, L., Uhlén, M
and Nygren, P.-Å. (2002) "Anti-idiotypic
protein domains selected from Protein A-based affibody libraries"
Prot. Struct. Funct. Gen. 48, 454-462. |
| • |
Rönnmark, J., Grönlund, H. Uhlén,
M. and Nygren, P.-Å. (2002) "Human
immunoglobulin A (IgA)-specific ligands from combinatorial
engineering of protein A" Eur. J. Biochem.
269, 2647-2655. |
| • |
Henning, P., Magnusson, M. K., Gunneriusson,
E., Hong, S. S., Boulanger, P., Nygren, P.-Å.
and Lindholm, L. (2002) "Genetic modification of adenovirus
5 tropism by a novel class of ligands based on a three-helix
bundle scaffold derived from staphylococcal protein A."
Human Gene Therapy 13, 1427-1439. |
| • |
Gräslund, S., Eklund, M., Falk, R.,
Uhlén, M., Nygren, P.-Å. and
Ståhl, S. (2002) "A novel affinity gene system
allowing protein A-based recovery of non-immunoglobulin
gene products" J. Biotechnol. 99, 41-50. |
| • |
Högbom, M., Eklund, M., Nygren,
P.-Å. and Nordlund P. (2003) "Crystal
structure of an in vitro evolved affibody-protein
complex" Proc. Natl. Acad. Sci. U.S.A. 100,
3191-3196. |
| • |
Wahlberg, E., Lendel, C., Helgstrand, M.,
Allard, P., Dincbas-Renqvist, V., Hedqvist, A., Berglund,
H., Nygren, P.-Å. and Härd,
T. (2003) "An affibody in complex with a target protein:
structure and coupled folding" Proc. Natl. Acad.
Sci. U.S.A. 100, 3185-3190. |
| • |
Rönnmark, J, Kampf, C., Asplund, A.,
Höidén-Guthenberg, Wester, K., I-M, Pontén,
F., Uhlén, M. and Nygren, P.-Å.
(2003)"Affibody-β-galactosidase immunoconjugates
produced as soluble fusion proteins in the E. coli
cytosol". J. Immunol. Meth. 281, 149-160. |
| • |
Sandström, K., Xu, Z., Forsberg, G.
and Nygren, P.-Å. (2003) "Inhibition
of the CD28-CD80 co-stimulation signal by a CD28-binding
ligand developed by combinatorial protein engineering".
Protein Engineering 6, 691-697. |
| • |
Nord, O., Uhlén, M. and Nygren,
P.-Å. (2003) "Microbead display of proteins
by cell-free expression of anchored DNA" J. Biotechnology
106, 1-13. |
| • |
Andersson, M., Rönnmark, J., Nygren,
P.-Å. and Ahlborg, N. (2003) "Inclusion
of a non-antibody binding protein in two-site ELISAs for
quantification of human serum proteins without interference
by heterophilic serum antibodies" J. Immunol. Meth.
283, 225-234. |
| • |
Eklund, M., Sandström K., Teeri, T.
and Nygren, P.-Å. (2004) "Site-specific
and reversible anchoring of active proteins onto cellulose
using a cellulosome-like complex" J. Biotechnol.
109, 277-286. |
| • |
Renberg, B., Nygren, P.-Å.,
Eklund, M. and Eriksson Karlström, A. (2004) "Fluorescence
resonance energy transfer-based detection of analytes using
anti-idiotypic affinity protein pairs" Anal. Biochem.
334, 72-80. |
| • |
Nord, O., Gustrin, A. and Nygren,
P.-Å. (2005) "Fluorescent detection
of β-lactamase activity in living E. coli via esterase
supplementation" FEMS Microbiology Letters
242, 73-79. |
| • |
Engfeldt, T., Renberg B., Brumer, H., Nygren,
P.-Å. and Eriksson Karlström, A. "Chemical
synthesis of fluorescent-labeled affinity proteins for specific
binding and detection of unlabeled protein" Chem.
BioChem. 6, 1043-1050. |
| • |
Renberg, B., Shiroyama, I., Engfeldt, T.,
Nygren, P.-Å. and Eriksson Karlström,
A. (2005) "Affibody protein capture microarrays: synthesis
and evaluation of random and directed immobilization of
affibody molecules" Anal. Biochem. 334, 72-80. |
| • |
Renberg, B., Nordin, J. Merca, A., Uhlén,
M., Feldwisch, J., Nygren, P.-Å.
and Eriksson Karlström, A. (2007) "Affibody molecules
in protein capture microarrays. evaluation of multidomain
ligands and different detection formats" J. Proteome
Res. 6, 171-179. |
| • |
Taussig MJ, Stoevesandt O, Borrebaeck CA,
Bradbury AR, Cahill D, Cambillau C, de Daruvar A, Dubel
S, Eichler J, Frank R, Gibson TJ, Gloriam D, Gold L, Herberg
FW, Hermjakob H, Hoheisel JD, Joos TO, Kallioniemi O, Koegl
M, Konthur Z, Korn B, Kremmer E, Krobitsch S, Landegren
U, van der Maarel S, McCafferty J, Muyldermans S, Nygren
P-Å, Palcy S, Pluckthun A, Polic B, Przybylski
M, Saviranta P, Sawyer A, Sherman DJ, Skerra A, Templin
M, Ueffing M, Uhlen M. (2007) "ProteomeBinders: planning
a European resource of affinity reagents for analysis of
the human proteome" Nat Methods 4, 13-17. |
| • |
Bandmann N. and Nygren P-Å.
(2007) "Combinatorial expression vector engineering
for tuning of recombinant protein production in Escherichia
coli" Nucleic Acids Res. 35(5):e32. |
| • |
Wagner S, Baars L, Ytterberg AJ, Klussmeier
A, Wagner CS, Nord O, Nygren P-Å,
van Wijk KJ, de Gier JW. (2007) "Consequences of membrane
protein overexpression in Escherichia coli"
Mol Cell Proteomics 6, 1527-1550. |
| • |
Jonsson, A., Dogan J., Herne, N., Abrahmsen,
L. and Nygren, P.-Å. (2008) "Engineering
of a femtomolar affinity binding protein to human serum
albumin" Protein Engineering, Design and Selection
(PEDS) 275, 2668-2676. |
| Reviews |
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Ståhl, S, Nygren, P.-Å.
(1997) "The use of gene fusions to protein A and protein
G in immunology and biotechnology" Patologie Biologie
45, 66-76. |
| • |
Nilsson, J. Ståhl, S., Lundeberg, J.,
Uhlén, M. and Nygren, P.-Å.
(1997) "Affinity fusion strategies for detection, purification
and immobilization of recombinant proteins" Prot.
Exp. and Purif. 11, 1-16. |
| • |
Nygren, P.-Å. and
Uhlén, M. (1997) "Scaffolds for engineering
novel binding sites in proteins" Curr. Opin. Struct.
Biol. 7, 463-469. |
| • |
Nygren, P.-Å., Ståhl,
S. and Uhlén. M. (1994) "Engineering protein
to facilitate bioprocessing" TIBTECH 5, 184-188. |
| • |
Nygren, P.-Å and Skerra
A. (2004) "Binding proteins from alternative scaffolds"
J. Immunol. Meth. 290, 3-28. |
| • |
Nygren, P.-Å. (2008)
"Alternative binding proteins: Affibody binding proteins
developed from a small three-helix bundle scaffold"
FEBS Journal 275, 2668-2676. |
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