- Startsida
- Units:
- MCG Unit
- ME Unit
- ACC Unit
- GTC Unit
- Core Facility:
- EGCF Facility
- EMIL Facility
- MAP Facility
- MAF Facility
- MSF Facility
- LF Facility
Unit for Molecular Cell Biology and Gene Therapy Science
Project 1 : Program in Cell Signalling
Our laboratory is studying cellular differentiation and the way this process is regulated by signal transduction. The main focus is on a cytoplasmic protein-tyrosine kinase (PTK); designated Btk. Btk belongs to the second largest family of mammalian PTKs, the Tec family (Smith et al., 2001). This kinase is affected in the disease X-linked agammaglobulinemia (XLA), and was identified as a result of positional cloning (Vetrie et al., 1993). It has many interesting features, including a pleckstrin homology (PH) domain located in the N-terminus providing membrane attachment. Btk was found to shuttle between the cytoplasm and the nucleus (Mohamed et al., 2000). One approach to understand the signalling process is to investigate structure-function relationships (Hansson et al., 1998; Fig. 1). Other approaches are also used in order to study signalling pathways, including cell biology, biochemistry, imaging, expression profiling, and siRNA technology (Fig. 2).
Fig. 1. Modified version of the NMR solution structure the Btk-SH3 domain as determined by Hansson et al., 1998.
Fig. 2. Plasmid-based siRNA silencing. Cells transfected with Btk-EGFP alone (A), or with specific siRNA (B). From Heinonen et al., 2002.
Selected references
Mohamed AJ, Vargas L, Nore BF, Bäckesjö C-M, Christensson B, Smith CIE. Nucleocytoplasmic shuttling of Bruton's tyrosine kinase. J Biol Chem 275:40614-40619, 2000.
Smith CIE, Islam TC, Mattsson PT, Mohamed AJ, Nore BF, Vihinen M. The Tec family of cytoplasmic tyrosine kinases: mammalian Bmx, Btk, Itk, Tec, Txk and homologs in other species. Bioessays 23:436-446, 2001.
Vetrie, D., Vorechovsky, I., Sideras, P., Holland, J., Davies, A., Flinter, F., Hammarström, L., Kinnon, C., Levinsky, R., Bobrow, M., Smith, C.I.E. and Bentley, D. (1993). The gene involved in X-linked agammaglobulinemia is a member of the src family of protein-tyrosine kinases. Nature 361, 226-233.
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Project 2 : Program in Gene Therapy
Gene therapy is an emerging technology with the potential of having an important impact on future treatment of human disease. The objective of our program is to develop a novel strategy for gene transfer (Fig. 3), designated Bioplex (Brandén et al., 1999, Brandén & Smith 2002). Bioplex is based on a new concept in which functional peptide entities are hybridised to plasmids by the use of peptide-nucleic-acids (a synthetic nucleic acid analogue). This allows specific anchoring to any target sequence. The aim is to develop nanomolecular complexes with an efficiency comparable to viral-mediated gene transfer, but with lower toxicity and immunogenicity. A candidate organ is the liver.
The Bioplex technology has the potential to bridge the gap in efficiency between plasmids and viruses. A start-up company, Avaris AB, being involved in the development of certain aspects of this technology was formed in 2001.
Fig. 3.Schematic representation of the Bioplex technology showing hybridisation of functional entities to a plasmid.
Selected references
Arteaga HJ, Hinkula J, van Dijk-Härd I, Dilber MS, Wahren B, Christensson B, Mohamed AJ, Smith CIE
Choosing CCR5 or Rev siRNA in HIV-1
Nature Biotechnology, March 2003, 21:230-231.
Brandén LJ, Mohamed AJ, Smith CIE. A peptide nucleic acid-nuclear localization signal fusion that mediates nuclear transport of DNA. Nature Biotechnol 17:784-787, 1999.
Brandén LJ, Smith CIE. Bioplex technology. A novel, synthetic gene delivery system based on peptides anchored to nucleic acids. Meth Enzymol 346:106-124, 2002.
Hansson H, Mattsson PT, Allard P, Hapaniemi P, Vihinen M, Smith CIE, Härd T. Solution structure of the SH3 domain from Bruton's tyrosine kinase. Biochemistry 37:2912-2924, 1998.
Heinonen JE, Smith CI, Nore BF. Silencing of Bruton's tyrosine kinase (Btk) using short interfering RNA duplexes(siRNA). FEBS Lett 527(1-3):274-8, 2002.
Mohamed AJ, Vargas L, Nore BF, Bäckesjö C-M, Christensson B, Smith CIE. Nucleocytoplasmic shuttling of Bruton's tyrosine kinase. J Biol Chem 275:40614-40619, 2000.
Smith CIE, Islam TC, Mattsson PT, Mohamed AJ, Nore BF, Vihinen M. The Tec family of cytoplasmic tyrosine kinases: mammalian Bmx, Btk, Itk, Tec, Txk and homologs in other species. Bioessays 23:436-446, 2001.
Vetrie, D., Vorechovsky, I., Sideras, P., Holland, J., Davies, A., Flinter, F., Hammarström, L., Kinnon, C., Levinsky, R., Bobrow, M., Smith, C.I.E. and Bentley, D. The gene involved in X-linked agammaglobulinemia is a member of the src family of protein-tyrosine kinases. Nature 361:226-233, 1993.
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Project leader
C. I. Edvard Smith
Professor, Unit chief
edvard.smith@ki.se
Phone +46-8-585 836 51
Fax +46-8-585 836 50
Senior Researchers and Postdoctoral Fellows
Karin Lundin, M.Sc., Ph.D.
karin.lundin@ki.se
Phone +46-8-585 836 63
Fax +46-8-585 836 50
Abdalla J. Mohamed, M.Sc., Ph.D., Associate Professor
abdalla.m.jama@ki.se
Phone +46-8-585 836 63
Fax +46-8-585 836 50
Beston F. Nore, M.Sc., Ph.D., Associate Professor
beston.nore@ki.se
Phone +46-8-585 839 90 (or 83657)
Fax +46-8-585 836 50
Leonardo Vargas, B.Sc., Ph.D.
leonardo.vargas@ki.se
Phone +46-8-585 836 56
Fax +46-8-585 836 50
José Arteaga, M.D., Ph.D.
jose.arteaga@ki.se
Phone +46-8-585 83806 (or 83812)
Fax +46-8-585 836 50
Maria Cardona, M.Sc., Ph.D.
Maria.cardona@ki.se
Phone +46-8-585 83806 (or 83812)
Fax +46-8-585 836 50
Faryal Faheem, M.Sc., Ph.D.
Faryal.fahim@ki.se
Phone +46-8-585 83806 (or 83812)
Fax +46-8-585 836 50
Anna Berglöf, V.M.D., Ph.D.
anna.berglof@ki.se
Phone +46-8-585 838 73
Fax +46-8-585 836 50
Research Assistant
A. Charlotta Asplund, B.Sc., Research assistant
lotta.asplund@ki.se
Phone +46-8-585 836 57
Fax +46-8-585 836 50
Ph.D Students
Emelie Blomberg, M.Sc., Ph.D. student
emelie.blomberg@ki.se
Phone +46-8-585 836 57
Fax +46-8-585 836 50
Rongbin Ge, M.D., Ph.D. student
ge.rongbin@ki.se
Phone +46-8-585 836 63
Fax +46-8-585 836 50
Juhana E. Heinonen, M.Sc., Ph.D. student
juhana.heinonen@ki.se
Phone +46-8-585 836 65 (or 83663)
Fax +46-8-585 836 50
Liang Yu, M.D., Ph.D. student
liang.yu@ki.se
Phone +46-8-585 836 63
Fax +46-8-585 836 50
Mathias Svahn, M.Sc., Ph.D. student
mathias.svahn@ki.se
Phone +46-8-585 836 52
Fax +46-8-585 836 50
Pedro Moreno, M.Sc., Ph.D. student
Pedro.moreno@ki.se
Phone +46-8-585 836 63
Fax +46-8-585 836 50
Maroof Hasan, M.D., Ph.D. student
Maroof.hasan@ki.se
Phone +46-8-779 35 00
Fax +46-8-585 836 50
Joana Viola, M.Sc., Ph.D. student
Joana.viola@ki.se
Phone +46-8-779 35 00
Fax +46-8-585 836 50
Sofia Stenler, M.Sc., Ph.D. student
Sofia.stenler@ki.se
Phone +46-8-585 836 86
Fax +46-8-585 836 50
Iulian Oprea, M.D., Ph.D. student
lulian.oprea@ki.se
Phone +46-8-779 35 00
Fax +46-8-585 836 50
Oscar Simonson, PharmD, Ph.D. and M.D. student
oscar.simonson@ki.se
Phone +46-8-585 836 52
Fax +46-8-585 836 50
Post Graduate Preparatory Ph.D. students
Hossain Nawaz, M.D., Ph.D. student
hossain.nawaz@ki.se
Phone +46-8-585 83806 (or 83812)
Fax +46-8-585 836 50
Alamdar Hussain, M.Sc., Ph.D. student
alamdar.hussain@ki.se
Phone +46-8-585 83806 (or 83812)
Fax +46-8-585 836 50