Ore 17,00 – In aula Magna dell’universirà, quarta conferenza della serie “Marco Fraccaro Lectures”, che il Collegio Cairoli ed il Collegio Volta dedicano congiuntamente alla memoria dell’insigne genetista prof. Marco Fraccaro (già titolare della cattedra di Biologia Generale e di Genetica Medica nella Facoltà di Medicina, Direttore dell’Unità di Biologia e Genetica del Dipartimento di Patologia Umana ed Ereditaria dell’Università di Pavia e Rettore del Collegio Cairoli dal 1969 al 2001).
La Marco Fraccaro lecture 2017, dal titolo “Gene targeting into the 21th century” è tenuta dal prof. Mario Capecchi, Nobel per la Medicina nel 2007.
The 2016/17 lecture will focus on gene targeting, an area of genetic research to which Mario Capecchi has made outstanding contributions that culminated in the award of the Nobel Prize for Physiology or Medicine in 2007. The poster of the lecture can be downloaded here.
To date, gene targeting has been used primarily to disrupt genes, producing so called knockout mice. However gene targeting can be used to alter the sequences of a chosen genetic locus in the mouse in any conceivable manner, thus providing a very general means for editing the mouse genome. It can be used to generate gain-of-function mutations or partial loss-of-function mu- tations. Gene targeting can also be used to restrict the loss of function of a chosen gene to particular tissues, yielding so-called conditional mutations. This is most commonly achieved by combining exogenous (nonmammalian) site-specific recombination systems, such as those derived from bacteriophages or yeast (i.e. Cre/loxP or Flp/FRT respectively), with gene targeting, to mediate excision of a gene only where the appropriate recombinase is produced. By control of where Cre- or Flp-recombinase is expressed, for example in the liver, a gene, flanked by loxP or FRT recognition sequences, respectively, can be excised in the desired tissue (e.g. liver) tempo- ral control of gene function has also been achieved by making the production of the functional recombinase dependent upon the administration of small molecules or even on physical stimuli, such as light. Such conditional mutagenesis has been very effective for more accurate modelingof human cancers, which are often restricted to particular tissues and even to specific cells within those tissue as well as being initiated post birth. Inhuman cancers, the interactions between the host tissues and the malignant cells are often critical to its initiation and progression. Thus, inclusion of these interactions in the mouse model also becomes critical if the mouse model is to accurately recapitulate the human malignancy. Gene targeting is an evolving technology and we can anticipate further extensions to its repertoire. To date it has been used primarily to perturb the function of one gene at a time. We can anticipate development of efficient multiplexing sys- tems that will allow simultaneous conditional or non-conditional modulation of multiple genes. We can also anticipate improvements in exogenous reporter genes with parallel improvements in their detection, particularly with respect to capture times, resolution improvements will undoubt- edly be necessary if this technology is to make significant inroads in addressing truly complex biological questions, such as the molecular mechanisms underlying higher cognitive functions in mammals.
M. Capecchi was born in Verona (Italy) in 1937. He graduated in Chemistry and Physics at the Antioch College in Ohio and completed a PhD in Biophysics at Harvard in 1967. He was an Associate Professor at Harvard until 1973 when he move to the University of Utah to take up the position of Professor of Biology, Cancer Science and Human Genetics. He was awarded the Kyoto Prize in 1996, the Franklin Medal in 1997, the National Science Medal in 2001 and Wolf Prize in 2002. He shared the 2007 Nobel Prize for Physiology or Medicine with Oliver Smithies and Martin Evans.
M. Capecchi. Gene targeting. Nobel Lecture (2007)