The previous chapter discusses the importance of glycoscience as it relates to the areas of health, energy, and materials science. This chapter describes a series of scientific questions in which glycoscience plays a central role. As in previous chapters, this list is not meant to be exhaustive but is meant to stimulate discussion and highlight the scale of progress that could be made in addressing a broad set of questions embraced not only by glycoscientists but also by the larger science and technology community. Although many of the sections pose questions immediately related to human health, addressing the core issues they raise can have relevance to other areas. Included are examples from the fields of energy and materials, and the committee invites the broader community to develop and embrace other possible challenges important to those subjects.
It is well accepted that “nothing in biology makes sense, except in the light of evolution.” But when it comes to glycans, very little is known about glycan diversification during evolution. Over three billion years of evolution has failed to generate any kind of living cell that is not covered with a dense and complex array of glycans. Why and how has evolution led to this diverse array of glycans, and what are some of their roles, for example, in determinants of host-pathogen recognition? Glycans on host cells may be targets for pathogen recognition, and glycans can undergo subtle changes that may allow evasion from a pathogen, even while preserving sufficient intrinsic function. Glycans appear to remain a preferred class of molecules for the cell surface given their tolerance of such subtle changes, while proteins appear to be somewhat less tolerant of sequence changes, which more frequently result in loss of structure or function. In some cases these changes can result in glycan polymorphisms in the population or even wholesale elimination of specific types of glycans from certain taxa. Once a type of glycan diversification has occurred in a particular species, it could then be recruited for other intrinsic functions, some of which may remain noncritical and some of which may become essential. Thus, glycan diversity may involve continuous evolutionary adaptation and diversification for the generation of intrinsic functions as well as co-evolution through interactions with pathogen and symbionts. Remarkably little is known about the evolutionary diversity of glycans in nature.