海角社区

Abstract:

The most prevalent form of DNA is the double helix (B-DNA), located in the cell nucleus. However, this versatile biopolymer can also take on other conformations, such as guanine quadruplexes or the i-motif, each of which has utility in biology or nanotechnology. A new conformation discovered in 2016 by the Sleiman group is in a class by itself. Indeed, the dA/CAR triple helix is distinguished by the fact that it incorporates the small molecule cyanuric acid with polyadenine. The incorporation of this molecule is possible because it has three faces that resemble thymine, which allows it to bind to the Franklin-Watson-Crick and Hoogsteen faces of adenine. Cyanuric acid acts as a glue between the adenines of different DNA strands, bringing them together in a DNA hybrid form.

It is this recent concept of DNA hybrids forms induced by small molecules that has been the focus of my PhD research. The dA/CAR DNA hybrid structure has three characteristics that are very different from other DNA configurations: it integrates a large number of small molecules in a supramolecular way; it self-assembles into long supramolecular fibers; and, as far as we know, it is not found in Nature. In this talk, we will demonstrate how we use each of these characteristics to expand the capabilities of DNA nanotechnology. We will end with a widening of the DNA hybrid chemical space with the newly discovered and still mysterious dA/X forms.

Come rediscover DNA from this new angle; see it deviate from its classical biological role to endorse a plethora of hybrid personalities each with their own use and charm.

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Bio:

Christophe Lachance-Brais did his bachelor in chemistry at the University of Montr茅al. As an undergraduate, he had the chance to learn through internships in the laboratories of Pr. Alexis Vall茅e-B茅lisle, Pr. Garry Hanan, Pr. Radu Iftimie and Pr. Mika毛l Doll茅. His studies ended in 2016 with an exchange at the 脡cole Polytechnique F茅d茅rale de Lausanne in Switzerland. For quality of his undergraduate dossier, he was awarded the Prestige prize and the Lucien-Pich茅 prize.

Following his bachelors, he spent 1 year tutoring chemistry, physics and mathematics in a juvenile readaptation center before starting a PhD in 2017 under the supervision of Pr. Hanadi Sleiman and funded by a Vanier scholarship.

The unifying thread of his doctoral research has been new induced forms of DNA and RNA. It was discovered that polyadenine can be reconfigured by the addition of small molecules mimicking thymine, resulting in the formation of unnatural hybrids. In collaboration with a diverse group of researchers, Dr. Lachance-Brais elucidated the thermodynamic and structural properties of these DNA hybrids. This investigation ruled out many proposed models for the hybrid structure, providing the best understanding to date of their assembly. Building on this fundamental understanding, Dr. Lachance-Brais created a method to protect DNA and RNA from biological degradation, as well as the stiffest hydrogels made of unmodified DNA to date, setting new benchmarks in the field. Combined, these led to a patent for a gene silencing DNA hydrogel. In addition to having expanded the application scope of DNA-hybrids, Dr. Lachance-Brais has expanded their chemical landscape by discovering an entirely new class of molecules capable of reconfiguring DNA into novel and exotic shapes. For his thesis entitled 鈥淣ucleic Acid / Small-Molecule Hybrids and Their Use in Supramolecular Functionalization, DNA Hydrogels, Gene Silencing, and Sequence Protection鈥�, he received his PhD in July 2023.

In his current postdoc position, he has moved to the University of Groningen in the Netherlands to work with Pr. Ben Feringa on using DNA nanotechnology to unite the motion of molecular motors.