Gene regulation of the immune system in Biomphalaria glabrata
The main goal of my research is to better understand how gene expression is regulated in immune responses in the snail Biomphalaria glabrata. This freshwater snail (B. glabrata) is typically studied because it is the intermediate host to a tropical parasite called Schistosoma mansoni , one of several species that cause the debilitating disease schistosomiasis in humans. This neglected disease is a major cause of morbidity in approximately 210 million people in 76 countries.
Fig. 1. General lifecycle of Schistosoma species from www.merckmanual.com
Whenever you have a cold or flu, genes encoding components of your immune system e.g. cytokines, are upregulated, so they are available in greater quantities to participate in the immune response. Studies suggest that the same happens when B. glabrata snails are infected with pathogens including S. mansoni. However, we do not know exactly how these changes in gene expression are brought about in B. glabrata.
Gene expression regulation is very complex and I have chosen to focus on just one component of this regulation, transcription factors. In order to regulate gene expression, transcription factors bind to specific genomic sequences or motifs and these motifs appear to be highly conserved across species. One group of transcription factors shown to participate in immune and inflammatory responses in both vertebrates and invertebrates is the nuclear factor kappa binding (NFκB) family. Therefore my lab is investigating whether the NFκB pathway is involved in the regulation of immune-related genes in B. glabrata.
We are also interested in a family of immune receptors called Toll-like receptors (TLRs) because in other species, the NFκB pathway has been found to work in conjunction with TLRs. We recently cloned and sequenced a TLR from B. glabrata and since then have been looking for additional members of the TLR-NFkB pathway in the snail (Fig. 2)
Fig. 2. Proposed TLR-NFκB pathway in B. glabrata
Neurobiology of B. glabrata
In addition to my primary research focus on the immune system of B. glabrata, I am also interested in the nervous system of both embryonic and adult snails. We have localized neurotransmitters such as serotonin and FMRFamide in the developing nervous system of embryos. Furthermore we identified a neuropeptide in the snail called neuropeptide Y (NPY) and we have shown it is present in abundance in the brains of adult snails (Fig. 3).
Fig. 3. NPY-immunoreactivity in the brain of adult B. glabrata