Extremely efficient biological catalysts known as enzymes have emerged from the evolutionary process after eons of selective pressures. Elucidating which residues are directly involved in the catalytic process is relatively straightforward, but this is not the case for residues which may facilitate catalysis from distal locations. Further muddling the issue, many distal residues have also evolved as part of epistatic networks enhancing such things as stability and multimerization. The design of miniaturized enzymes around a hypothesized catalytic chassis should therefore allow a deeper investigation into the function of these residues, or the lack thereof.

Dr. Nicolas Doucet

Prediction and characterization of synthetic galectins: cutting-edge analysis powered by artificial intelligence

Galectins are proteins that play critical roles in important biological processes, and some of them have been associated with life-threatening pathologies. Although different galectins generally participate in distinct biological processes, their comparable affinity and structural homology make it challenging to develop specific functional modulators. This can lead to off-target inhibition of beneficial homologous galectins. To specifically target galectins involved in selected pathologies, deciphering their unique mechanism of action at the molecular level is warranted. With the exponential advancement in machine learning, emerging bioinformatics tools promise unparalleled reliability in predicting the relationship between a protein structure, its function, and its dynamics. ProGen, an unsupervised machine learning algorithm, is at the forefront of this progress. It generates stable and functional synthetic protein sequences using a vast database of over 280 million natural protein sequences. Applying this algorithm to designing synthetic galectins will allow us to develop new stable and functional galectin models, providing an increased and peerless understanding of the structure-function-dynamics relationship in natural galectins. These synthetic galectins could also be used to modulate natural or pathological biological processes, particularly by using them as competitive inhibitors.

I enjoy playing music (piano, guitar and drums), crafting random things, learning anything science-related and trying new ways to express my creativity.

Laval, Québec, Canada

Dr. Andrew Woolley

Development of single component optogenetic tool by engineering binding activity in Photoactive Yellow Protein (PYP)

Classical optogenetic tools utilize a photosensitive proteins and their natural or engineered ligands as fusion partners to cellular proteins of interest to impart control of protein co-localization and activity using light. However, a key disadvantage of such an approach is that it cannot be used to inhibit the function of endogenous proteins that are not fused with a photosensitive protein or ligand, which might affect native interactions. Instead, we are proposing to engineer binding activity directly into a photoswitchable protein called PYP, which will allow light- sensitive activity control without the need for a fused protein. This can be achieved using combinatorial phage display libraries and in vitro screening.

Painting, Reading and Volunteering.

Calgary, Alberta, Canada

Dr. Elizabeth Meiering

Unraveled - Identification of Aggregation Initiators in ALS-linked SOD1 Mutants

Protein aggregation is of central importance in human health and in the ongoing development of protein-based products. Though aggregates are generally known to form from misfolded or disordered proteins, the specific molecular mechanisms and factors leading to aggregation remain obscure. The metalloenzyme superoxide dismutase 1 (SOD1) is an attractive model protein for investigating aggregation mechanisms, as many toxic aggregate-forming mutants of SOD1 are strongly associated with familial amyotrophic lateral sclerosis (fALS). At the Meiering Lab, different forms of SOD1 variants are being engineered and investigated under various conditions. Using a combination of experimental and computational techniques, we aim to determine labile structural regions that potentially hold critical roles in aggregation mechanisms, as well as to elucidate distinct mutation-induced aggregation pathways. The insights gained from our research will provide a firm basis for future protein designs to further define and, ultimately, control aggregation.

Writing poetry, listening to and making music, reading, watching video essays, fashion illustration, occasional arts and crafts.

Ho Chi Minh City, Vietnam