Ph.D Thesis

Ph.D StudentShoshani Sivan
SubjectNovel Applications of Molecular Computing Devices
DepartmentDepartment of Biotechnology
Supervisors PROFESSOR EMERITUS Ehud Keinan
PROF. Shmuel Wolf
Full Thesis textFull thesis text - English Version


Molecular computing is a growing area at the intersection of chemistry, molecular biology and computer science. A molecular computing device is a machine whose all four essential components - hardware, software, input and output - are represented by macromolecules. When mixed together in a solution, these macromolecules are capable of performing a computational task by a cascade of chemical events based on a programmed pathway. The research presented in this thesis is divided into three parts and demonstrates many of bio-molecular computing (BMC) advantages.

The first part of this dissertation presents the use of parallel computing with molecular finite-state automata and fluorescently labeled DNA molecules for deciphering two different images. Both logos of the Technion and The Scripps Research Institute were encrypted on a single DNA microarray chip. To decipher any of these images, a mixture of input molecules was processed by a given automaton, which led to image visualization by fluorescent, surface-bound output molecules. This is the first demonstration of a cryptosystem based on BMC.

The second part of this research was aimed at developing an automata-based BMC device capable of operating within a cellular environment. As a step towards achieving a full in-vivo computing system, we showed that the expression of a fluorescent protein in live plant cells can be utilized as a highly accurate output of a DNA-based computing. Each of the two possible in-vitro molecular results of a 2-symbol 2-state finite automaton led to the creation of a circular plasmid that contained the gene of either green fluorescent protein (GFP) or cyan fluorescent protein (CFP). Insertion of these plasmids into onion cells by particle bombardment resulted in either green fluorescent or cyan fluorescent live cells as phenotypical output signals. The plasmid formation served as a quality control gate that transformed a rather noisy output into a clean signal.

The third part of this research aimed at establishing the basic principles of in-vivo computing, thus opening the door to many attractive opportunities. We showed a design of a system suitable for operation in a cellular environment, namely, inside a living cell or in a cell lysate and the development of a detection method based on a new design of a molecular beacon. Preliminary results showed that this unique phenomenon might be suitable for molecular computing. Nevertheless, more work is needed in order to fully optimize the computing process for in-vitro use and for incorporating this system in-vivo.