Talk 1 Deep screening of biomolecular repertoires Talk 2 DNA-templated conjugation and assembly of molecular components

Talk 1 Deep screening of biomolecular repertoires
Massively parallel assays potentiate both scale and speed of data generation in the biomedical sciences and have proven key to the discovery of antibody, peptide, aptamer leads as well as enzymatic catalysts. While repertoire generation by high-throughput DNA oligonucleotide synthesis is highly developed, and selection strategies (such as phage, yeast & ribosome display) are able to process very large combinatorial (poly)peptide repertoires, these only reveal a highly biased section of the possible genotype / phenotype space.
We have developed deep screening, an ultra-high-throughput approach that leverages the power of the Illumina HiSeq platform for massively parallel sequencing, display, and global screening of diverse biomolecular repertoires.
Deep screening enables the real-time examination of both binding interactions and catalysis in repertoires of RNA, XNA (xeno nucleic acids), peptide and nanobody (VHH) and single-chain Fv (scFv) antibody sequences at a depth of up to 109 individual, simultaneous measurements, enabling the discovery of antibodies with picomolar target affinities in a 3-day experiment directly from synthetic repertoires.
The very large genotype-phenotype correlation datasets generated by deep screening combined with transformer machine learning models enable rapid, in silico prediction of novel and highly functional antibody sequences not present in the original repertoires and promise to further accelerate antibody discovery for a wide range of drug targets.
We anticipate many applications of the deep screening platform in particular the accelerated discovery and development of antibodies and aptamers for biotechnology and medicine.

Talk 2. DNA-templated conjugation and assembly of molecular components
Nature displays exquisite control over organizing and assembling molecules into complex nanostructures with active and specialized functions. That level of control remains a challenge for our ability to build synthetic molecular complexes with specialized and custom functions. These complexes require absolute control over the fabrication process including the integration of heterogeneous components and their positioning with near-atomic precision.
In the seminar, I will present a templating technique1 for the efficient attachment of two different oligonucleotides (adapters) to homobifunctional organic molecules, enabling its controlled and programmable placement within a DNA nanostructure. This technique was applied to a range of organic molecules with different conjugation chemistries and water solubilities.
Provision of two unique adapters allows the assembly of devices with heterologous molecules as functional components with precise control over both the position and orientation of a heterologous molecule. I will also present results on using this technique for two applications where the ability to manipulate and orient single molecules is required: positioning of molecular components in DNA-templated molecular integrated electronics, and assembly of DNA motors using photoactivated molecules to drive rotation.