Astrid Gräslund教授简介
Education: High School graduation at Högre Allmänna Läroverket in Härnäsand, April 21, 1963 Master of Science in Engineering (Applied Physics) at the Royal Institute of Technology, Stockholm, October 30, 1967 Doctor of Philosophy (Biophysics) at Stockholm University, November 29. 1974
Employments: Research assistant at Dept. of Biophysics, Stockholm University, 1967 - 1976 Assistant/associate professor at Dept. of Biophysics, Stockholm University, 1977 – 1988. Professor of Medical Biophysics, University of Umea, 1988 – 1993. Professor of Biophysics, Stockholm University, since 1993. Chairman of the Department of Biophysics, Stockholm University, 1993 – 2000. Chairman of the Department of Biochemistry and Biophysics, Stockholm University, since 2006
Honors: Received the 1982 Lindbom Prize awarded by the Royal Swedish Academy of Sciences.
Received the 1995 Arrhenius Plaque, awarded by the Swedish Chemical Society. Received the 2007 Björkén Prize, awarded by Uppsala University
Activities:
Chairman of the Swedish Biophysical Society 1987-1992. Visiting scientist March – May 1987 at the Dept. of Biophysical Chemistry, University of Nijmegen, Nijmegen, The Netherlands. Visiting scientist Sept. 1987 – March 1988 at the Dept. of Chemistry and Biochemistry, Southern Illinois University, Carbonale, Illinois, USA. Visiting scientist October 2002 - April 2003 at The Scripps Research Institute, La Jolla, California, USA.
Member of the Board of the Magn. Bergvall Foundation. Member of the Editorial Board of Accounts of Chemical Research.
Member of the Editorial Advisory Board of Biochim. Biophys. Acta (Biomembranes)
Member of the Council of IUPAB (Int. Union of Pure and Applied Biophysics) 1996-2002. Member of the Swedish Natural Science Research Council (NFR), 1995-2000. Member of the Royal Swedish Academy of Sciences, Class of Chemistry, since 1993. Second Vice President of the Royal Swedish Academy of Sciences, 2000 - 2002. Secretary of the Nobel Committee for Chemistry, since 1996.
Deputy member of the Board of the Nobel Foundation, since 2007.
Scientific publications: Ca 280 scientific publications in molecular biophysics.
Cell penetrating peptides – mechanisms and biology
A. Gräslund
Dept. of Biochemistry and Biophysics, Stockholm University,
SE-10691 Stockholm, Sweden
Cell penetrating peptides (CPPs) are short (<30 amino acids), cationic, partly hydrophobic, and/or amphipathic peptides, which can carry large hydrophilic macromolecules across cellular membranes and exhibit low cell toxicity. Their mechanisms are under debate, and may vary between peptides and depend on cargo. More than one may be active. Among mechanisms under discussion are:
* Endocytosis – often macropinocytosis via proteoglycans (heparan sulphate) on cell surface, followed by endosomal escape inside cell. Also clathrin mediated endocytosis has been reported. Endocytotic mechamisms dominate for very basic peptides like Tat and oligoR, and peptides with large cargoes.
* Direct membrane interaction – related to pore formation by antibacterial peptides: ”membrane thinning”, ”carpet model”. These mechanisms may contribute for more toxic but highly efficient CPPs like transportan, perhaps only with smaller cargoes. This process is also related to endosomal escape after endocytosis.
The lecture will describe some biophysical studies of CPPs interacting with model membranes, and relate the results to the discussion of CPP mechanisms.
I will also describe some biological systems where CPP properties of native molecules may contribute to biological effects: the dynorphin neuropeptides and the prion protein. |