Ndeh, Didier

My lab aims to understand the genetic and molecular basis of complex glycan metabolism and function in health and disease and how this knowledge can be exploited to improve plant, microbial, human health and the bioeconomy. To achieve this, we apply a variety of techniques in carbohydrate chemistry, enzymology, genetics, structural biology, microscopy and bioinformatics.

Background and current projects

Glycans are present in almost all life forms including plants, animals and microbes. They exhibit remarkable structural diversity and complexity, enabling them to participate in a variety of critical physiological and pathophysiological processes including cell signalling, growth, development, infection, metastasis, immunity, nutrition and disease. The importance of glycans is also exemplified by the fact that their exploitation has led to the development of several high value biologicals including therapeutics, vaccines, drug delivery systems, diagnostics and other glycan-based commercial products such as gelling agents, thickening agents, animal feeds and biofuels which have greatly enhanced human, plant health and the bioeconomy. Glycan research is however greatly hampered by glycan structural complexity, limited knowledge of glycan metabolism and function and availability of methods and enabling tools. These in turn limit our ability to exploit the full potential of glycans.  Focusing on some of nature’s most complex glycans, my group is currently developing new genetic/biochemical tools and approaches to enable us to address these important limitations. Some current projects include;

A microbial glycan production platform for glycoscience research. Glycoscience  research is greatly hampered by lack of  enabling tools including chemically defined glycan/glycoconjugates to probe glycan-active proteins. This limitation has hindered progress in the development of glycan-based therapeutics, nutraceuticals, vaccines, diagnostics, and other industrially relevant biologicals. In this light, we are working together with chemists and glycobiologists to develop glycan production/analytical platforms and tools that will enable us to address this problem, enabling us to expedite glycoscience research to the benefit of the bioindustry and human health.

Understanding the structure, metabolism and function of complex plant cell wall carbohydrates in health and disease. Complex plant cell wall carbohydrates  play a critical role in plant growth, development and protection of the plant from abiotic and biotic stresses from plant pathogens. Our lab uses a combination of biochemical, genetic, spectroscopic approaches to gain new insights into the fine  chemical/structural details of complex plant cell wall glycans and how these impact their function. These techniques also allow us to gain in-depth knowledge about metabolic pathways responsible for  their biosynthesis/assembly, transport, remodelling and degradation complex by host plant and plant-colonising microbes.  These studies will inform future crop engineering and improvement strategies and the production of next generation glycan-based health products.

Metabolism of complex glycans by the human gut microbiota. The human gut harbours a complex community of diverse microbial species, the human gut microbiota (HGM), whose activities greatly impact human health and disease status.  Its role in human health is further reinforced by several lines of evidence highlighting strong links between HGM composition and important human conditions such as obesity, cancer, diabetes, autoimmune arthritis and inflammatory bowel disease. Complex glycans, most of which are derived from dietary plant cell wall material are a major source of nutrients for the HGM. Understanding how the HGM interacts and metabolises these complex glycans could therefore inform pre-, probiotic and other therapeutic strategies to manipulate the HGM for human health benefit.

Discovery and Structural Biology of Glycan or Carbohydrate-Active Enzymes (CAZymes). The discovery of novel enzymes is critical in the fight against plant and human diseases, the reduction of fossil fuel use and provision of clean energy. We have a strong record of discovering several novel carbohydrate-active enzymes, ranging from glycoside hydrolases (e.g., GH137, GH138, GH141), carbohydrate esterases (e.g., CE19), to polysaccharide lyases (PL29) through the mining of metagenomes and microbiomes. We also study the structure and molecular basis of their catalytic activities and applications.