Pier Luigi Luisi Synthetic Biology Lab
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History of the Research in the Luisi Lab

Pier Luigi Luisi came to the ETH-Zürich in 1970 and developed here his professional career, becoming ordinarius in “Macromolecular Chemistry” in the early 80ties.
His group was located within the Institute of Polymers (“Institut für Polymere”, IfP), which he helped grounding together with Prof. Piero Pino (his mentor) and Prof.
Joachim Meissner, an Institute which is now part of the department of Materials Sciences of the ETH-Zürich.
Within IfP, Luisi developed a “Biopolymer group” at the interface between the Department of Materials Sciences and the Department of Chemistry. Luisi was the Chair (“Vorsteher”) of the Chemistry Department in 1996-1998.

Initially (1970-1980), the research activity of Luisi’ group concerned with the synthesis and conformation of peptides (Rizzo & Luisi,1977; Rizzo et al,1977; Skrabal et al,1979; Wolf & Luisi,1979). Peptides were also prepared by the help of proteases by reverse hydrolysis reactions (Anderson & Luisi,1979; Luisi et al, 1979).
In these first years also the study of the mechanism of action of dehydrogenases was in the focus of the research activity (Joppich-Kuhn & Luisi,1978 ; Abdallah et al, 1978).
In the field of enzymology, the group developed new techniques of rapid kinetics (stopped-flow), as well as of fluorescence.

A second phase of the work of the group started in 1980 ca. and concerned the self-assembly of surfactant aggregates.
The interest for this field can be understood on the basis of the illustration below:

To this period belong the studies on enzymes in reverse micelles, a field on which the group has done pioneering work.
Some of the most cited references of Luisi’ group still go back to this period ( Grandi et al, 1981; Luisi & Laane, 1986; Luisi & Majid, 1986; Luisi & Straub,1984; Luisi et al,1988).
In this period, Peter Walde joined Luisi’s group and his collaboration was instrumental in developing the field of enzymes in reverse micelles, self-reproduction of micelles, and later on the field of vesicles.
The field of reverse micelles (RM) was typically at the interface between basic science and biotechnology (applications of enzymes or protein separation (Pfammatter et al, 1992) and/or micro-organisms in organic solvents(Pfammatter et al,1992; Famiglietti et al,1992).
Also DNA as well as plasmids or entire ribosomes could be brought into the water pool of RM (Imre & Luisi,1982 ; Palazzo & Luisi,1992).

The work on reverse micelles brought by serendipity to the discover of lecithin organogels (Scartazzini & Luisi,1988; Capitani et al,1988; Haering & Luisi,1986; Schurtenberger et al,1989) which were developed into patents.
Lecithin organogels have been studied in the group as matrices for the transdermal transport of drugs (Willimann et al,1992; Willimann & Luisi,1991) in collaboration with the pharmaceutical Company Inpharzam/Zambon at Cadempino, Switzerland.
The structure of lecithin gels has been then studied independently by Peter Schurtenberger’s group, initially located within Luisis’ group and now professor of physical chemistry at the University of Fribourg, Switzerland.

To this second phase belongs also the work on cubic phases, which were studied as transparent matrices for proteins (Portmann et al,1991; Landau & Luisi,1993) This work was later on developed independently by Dr. Ehud Landau at the Biozentrum in Basel.

The interest of Luisi for biological question brought to a collaboration with Francisco Varela, the proponent (together with Humberto Maturana) of the notion of autopoiesis.
A first theoretical paper on self-reproduction autopoietic models based on micelles was developed (Luisi & Varela, 1990), which was actually the origin of the studies of the group on origin of life and self-reproduction. The theory of autopoiesis has been extended by us so as to develop a minimal chemical autopoietic system (Bachmann et al, 1990; Luisi,1993 ; Bachmann et al,1992).

In this relation, we have been involved in a study of the definitions of life (Luisi,1998) as well as in a study of the relation between the RNA-world approach to the origin of life vis-a-vis the membrane-compartimentation approach (Luisi,1993; Luisi,1997; Luisi, 2000; Luisi et al,1999).

The main research activity of the group since ca. 1990 focuses on vesicles and liposomes and their biological relevance, both in fundamental and applied science. In particular, we are now known as one of the few European chemistry groups working in the area of the origin of life.

The group consists now, in addition to Pier Luigi Luisi, of three senior researcher, Peter Walde who obtained the title of Titular-Professor of the ETH-Z in 1997; Matthias Voser, who is responsible of the molecular biology in liposomes, including the project on minimal cell (see below); and Richard M. Thomas who is a biophysicist specialized in the application of spectroscopic techniques, including ultracentrifugation. The group enjoys the secretary help of Mrs. Margrit Zeller and has in average 1-2 postdocs and 8-9 graduate students (Doktorandinnen und Doktoranden).

Pier Luigi Luisi is also responsible of the initiative Cortona-Week (Cortona-Woche) , a program developed at the ETH-Z to foster the interdiscliplinarity and the integration between science and humanities for academic students and teachers.

The study of the origin of life is tantamount to the study of the origin of molecular complexity - how the complex structures of life - enzymes, nucleic acids, the cell, may have arisen from the very simple organic and inorganic molecules that were produced on our Earth by natural processes.
Lipids, lipid aggregates and in particular liposomes are used in our group under the working hypothesis that these self-organized, compartmentalised structures may contribute to the construction of higher molecular complexity.

In particular, two complementary lines of research are followed in the group, which are defined as bottom-up and top-down approaches to the origin of life. In the bottom-up approaches, we start from very simple, possibly prebiotic molecules, with the goal of increasing step-wise the molecular complexity-up to tendentiously reaching a working protocell.
In this approach enzymes and nucleic acids cannot be utilised, - as they were not existing at the beginning of the prebiotic history. This approach, by which an increasing degree of complexity and function specificity is obtained by progressive increase of the molecular complexity, corresponds philosophically to the notion of emergence: about this notion Pier Luigi Luisi has written an extensive review (in press in “Foundation of Chemistry”).



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