SELEX for synthetic biology and nanoscale applications

Prof. Dr. Rolf Backofen (Department of Computer Science, University of Freiburg)

Dr. Jianying Yang (Biology III, Faculty of Biology, University of Freiburg)

Aptamers (from the Latin aptus - fit, and Greek meros - part) are single-stranded oligonucleotide that bind to protein or other target with high specificity and affinity. Aptames can be easily incorporated into sophisticated synthetic biotools such as Riboswitchs as a sensor module. Due to its small size and high affinity, Aptamers are also better reagents for labeling target proteins in nanoscale analysis. Aptamers can be developed against virtually any target through an in vitro selection process known as SELEX (systematic evolution of ligands by exponential enrichment). To find aptamer candidates, the traditional random cloning and sequencing approaches only enable sampling of a small portion of the enriched sequences, thus it is often needed to perform the SELEX with more than 20 rounds to allow enough convergence of the library.  

With this BIOSS-2 project, we aim at developing more efficient SELEX strategy by combining the power of next generation sequencing and bioinformatics analysis. We will also incorporate iCLIP method to SELEX for mapping the nucleotides involved in binding. Sequencing of early rounds of SELEX will be used to determine the enrichment of (sub-)sequences and their associated properties by means of  clustering according to sequence and structure. For this problem, we will use GraphClust developed by the Backofen group, which is one of the most advanced clustering approaches and currently the only available approach for a large-scale clustering of RNA-sequences.