Glycans play critical roles in various biological processes

(some components of this figure have been taken from Wikimedia Commons)

The SimBioSys Group currently focuses on the study of glycoproteins and other densely glycosylated systems. Glycans (branching polymers of pyranose sugars) play critical roles in a large number of biological processes, therapeutics, and biomedical devices. However, they are extremely refractory to experimental studies due to their heterogeneous structures and complex dynamics, The main thrust of this lab is on (i) developing new methods, as well as (ii) applying existing techniques to elucidate the roles of glycoproteins in devastating diseases, and harness these systems for better treatment strategies.

Towards improved Viral Immunogen Design

Spike proteins expressed on the surface of enveloped viruses are important targets for vaccine design. However, these proteins are usually densely glycosylated, acting as a physical shield from antibody binding. Alternately, in some cases, the antibody response may evolve to incorporate the glycans within the epitopes. Our group is investigating such viral antigen-antibody interactions while considering multi-scale dynamics of the glycans at the interface. This research builds on our prior work of glycan modeling toolsets that include (i) pipeline for glycan ensemble modeling; (ii) network analysis of inter-glycan interactions; (iii) topological quantification of glycan shielding; (iv) coarse-grained parameterization of glycans. The target is to elucidate detailed interactions between epitope-paratope complexes and predict improved immunogen design.

(one component of this figure has been taken from Wikimedia Commons)

Investigating mucin-associated cancers

Aberrations in protein glycosylation patterns are ubiquitous to various forms of cancer. Of these, a key player is the densely glycosylated mucin protein, normally expressed on the epithelia and acting as a protective barrier from toxins and pathogenic microbes. Alterations to mucin glycosylation are associated with inflammation and malignancies. Sensitivities of mucin-based immunotherapy epitopes also depend on this glycan coverage. Consequently, a detailed comprehension of their three-dimensional structure, dynamics and electro-mechanical properties is essential for understanding the molecular basis of related tumor progressions. Our lab is currently focusing on developing methods for modeling such densely glycosylated mucosal layers, towards the goal of leveraging these models for mucin-based therapeutic strategies.

Computational modeling of glycan microarrays

Glycan microarray is a modern assay and biosensing technique based on an arrayed stratum of glycans acting as a screening layer for glycan binding proteins, antibodies, bacteria and viruses. This up and coming method coupled with fluorescence signaling is a high-throughput detection technique. However, much progress still needs to be made in terms of understanding the mechanical and electrochemical nuances that can lead to improved binding and detection. We are working towards obtaining a molecular level understanding of the implications of glycan types, densities and clustering towards assay response.

(some components of this figure have been taken from Wikimedia Commons)