- Paleobiochemical analyses of heme peroxidases

- Evo-Devo study into the origin and evolution of the major tissues and organs in the animalia

 See the list of this group's collaborators here !

Paleobiochemical analyses of heme peroxidases

PhD Student: Noeleen LOUGHRAN

Project description: The mammalian heme peroxidases (MHPs) are a medically important group of enzymes. Included in this group are myeloperoxidase, eosinophil peroxidase, lactoperoxidase, and thyroid peroxidase. These enzymes are associated with such diverse diseases as asthma, Alzheimer's disease and inflammatory vascular disease. Despite much effort to elucidate a clearer understanding of the function of the 4 major groups of this multigene family, we still do not have a clear understanding of their relationships to each other. We demonstrate, using a root mean squared deviation statistic, how the removal of the fastest evolving sites aids in the minimization of the effect of long branch attraction and the generation of a highly supported phylogeny. Based on this phylogeny we have pinpointed the amino acid positions that have most likely contributed to the diverse functions of these enzymes. Many of these residues are in close proximity to sites implicated in protein misfolding, loss of function or disease. We are verifying their functional significance in vitro using biogenesis studies and inflammatory response models. In this project we have also applied computational methods for the resurrection of ancestral heme peroxidases with the purpose of defining and modeling novel thermostable enzymes. This project and its paleobiochemcial approach to understanding and improving enzyme function has both fundamental and applied scientific outcomes.

 Evo-Devo study into the origin and evolution of the major tissues and organs in the animalia

PhD Student: Thomas WALSH

Project description: The animalia are a diverse group, including water-, land- and air-living species. Adaptation to this wide variety of niches has resulted in the development of the lung and lymphatic tissue to mention a few. What has governed these adaptations remains unknown but is likely to be a combination of events such as gene duplication and differential retentions and losses in different lineages, protein functional shift and regulatory region modification. In this project we focus on genes of specific relevance to organogenesis/tissue-genesis and maintenance. Homologs for these proteins are identified across all species from the animalia (for whom there are completed genomes).  By studying patterns of gene duplication and loss and mutation rate variation in both coding and noncoding regions of these protein families we can identify those events that coincide with the emergence of these tissues/organs in the fossil record. Precise timing of all tissues/organs and expansions/contractions/functional shifts in protein families will be performed. This research is central to our understanding of organ evolution and development, e.g. lymph, brain, lung and eye, in the animal kingdom and therefore understanding cancers and genetic disorders of these organs.