One of the major stumbling blocks in the field of origin of life is the understanding of the specificity sequence of enzymes and nucleic acids- how particular sequences endowed with particular functions have been selected out of the astronomic number of possibilities (20n for a polypeptide with polymerisation degree n). One important idea in this context is the following: that the functionality is associated with the chain folding, namely with a stable tertiary structure.The consequence of this idea is that selection could save only the folded chains, and that folding is then the pre-requisite for functionality, e.g. enzymic activity. 
However also from the experimental point of view, the problem appears very difficult because in practice we do not even  know any prebiotic polymerisation process that allows one to prepare co-polypeptide chains of 100 or so and containing many different aminoacids in the same chain. (the Merrifield method cannot be considered a prebiotic technique). Even assuming that such polymerisation methods were possible under prebiotic conditions, how then could the selection take place?
 

This is the question that we tackle in this project. This project has in fact two working directions, which reflect the two possible answers that we give to this question.
One type of answer foresees a random polymerisation and a corresponding huge number of chain products. To this random library of polypeptide chains selection rules were instrumental to filtrate out only a few samples. This is illustrated above. 
The second approach  is to conceive first the formation of a large number of shorter chains (decamers or so), and to invoke a prebiotic fragment condensation that brought about an increase of the chain length simultaneously with the eliination of the largest part of the products (e.g., due to solubility or to instability effects).Eventually, the, only a few folded samples could be selected out. 
 

Both projects were initiated in our group in the year 2000. In the first project, the random library of many polypeptide chains is obtained by athe technique of phage display (this is of course no prebiotic technique, but it offers a bypass to the problem of producing a large initial library of different chains). In this project, there is a team composed by dr. Wim Vrijbloed of the University of Zürich, dr. Richard Thomas and graduate student dr. Cristiano Chiarabelli.  Until now, it has been possible to set up the technique  for the production of random 40.mer polypeptides; as well an enzymatic technique to recognize and select the folded sequences.

The second project is carried out by graduate student dr. Salvo Chessari under the supervision of Richard Thomas. It was possible until now to synthetize by an automatic synthetizer one randomly conceived decapeptide, and attempts are now in progress to link covalently the two decamers by the classic method via a cysteine coupling reaction.