Research in the Ratner Lab


New Technologies for Glycomics

  Advances in carbohydrate chemistry are beginning to spin-off new biophysical methods to study glycoconjugates and their many roles in biology.  At the forefront of these new tools is the carbohydrate microarray – a method based on the functionalization of surfaces with natural and synthetically-derived glycans.  Drawing upon the strengths of its DNA and protein predecessors, the glycochip’s popularity is due primarily to its promise as a platform for high-throughput screening of glycan binding partners. 
  Carbohydrate-mediated adhesion frequently involves low affinity interactions.  Therefore, a carbohydrate microarray must display the glycan in a fashion that is readily accessible to interrogating biomolecules and the system must have low non-specific adsorption of analyte to non-binding glycans or underivatized portions of the array.   However, like other array-based technologies, little is known about the effects of surface chemistry, method of immobilization, density of attached glycan, and glycan accessibility on microarray performance.  By exploring these surface chemistries and characterizing arrays using modern surface analytical techniques, the Ratner Lab is focused on advancing glycoarray research.

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  Pathogens—including protists, bacteria and viruses—are among humanity's most significant and worthy adversaries.  A great deal can be learned about fundamental biological processes by studying these supposedly simple organisms.  Our lab is interested in developing new tools to study the roles played by glycans in mediating adhesion between pathogen and host.  The ultimate goal of studying host-pathogen interactions is to design new means for disrupting pathogenesis.

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  Nature has a great deal to offer when it comes to novel biomaterials.  An especially remarkable material made by many pathogens is the cyst wall biopolymer, a natural stealth biomaterial.  Many protozoan pathogens encyst to form a resilient and infectious cyst or spore, including Giardia, Entamoeba, Toxoplasma, Cryptosporidium, Acanthamoeba, Microsporidia and Cyclospora.  A mixture of carbohydrate and protein polymers, the cyst or oocyst wall protects the parasite during its passage between hosts, resisting bacterial degradation, shielding the cell from the hydrolytic environment of an animal’s digestive tract, and evading host immunity prior to excystation.   Our lab is studying these biopolymers with an eye for designing materials based on their unique properties and composition.

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  Cells interact with their environment via cell surface and secreted proteins.  Posttranslational modifications (PTMs) involving carbohydrates are nearly ubiquitous among this class of proteins.  These glycans can be used in proteomics studies as molecular biomarkers, providing a window into the proteins involved in intercellular interactions, wound healing, differentiation of tissues, pathogen virulence and host-pathogen interactions.  By increasing our sensitivity to cell surface and secreted proteins, glycoproteomics facilitates the rapid identification of key effector molecules.  Utilizing mass spectrometry, our lab is identifying carbohydrate-modified proteins as related to infectious diseases.  This research is being used to develop an understanding of enteric pathogens, provide candidates for diagnostics and vaccine development, and to illuminate the molecular mechanisms of infection.

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© 2007 Daniel M. Ratner