The Cryptosporidium parvum Kinome

<p>Abstract</p> <p>Background</p> <p>Hundreds of millions of people are infected with cryptosporidiosis annually, with immunocompromised individuals suffering debilitating symptoms and children in socioeconomically challenged regions at risk of repeated infections. There is currently no effective drug available. In order to facilitate the pursuit of anti-cryptosporidiosis targets and compounds, our study spans the classification of the <it>Cryptosporidium parvum </it>kinome and the structural and biochemical characterization of representatives from the CDPK family and a MAP kinase.</p> <p>Results</p> <p>The <it>C</it>. <it>parvum </it>kinome comprises over 70 members, some of which may be promising drug targets. These <it>C. parvum </it>protein kinases include members in the AGC, Atypical, CaMK, CK1, CMGC, and TKL groups; however, almost 35% could only be classified as OPK (other protein kinases). In addition, about 25% of the kinases identified did not have any known orthologues outside of <it>Cryptosporidium spp</it>. Comparison of specific kinases with their <it>Plasmodium falciparum </it>and <it>Toxoplasma gondii </it>orthologues revealed some distinct characteristics within the <it>C. parvum </it>kinome, including potential targets and opportunities for drug design. Structural and biochemical analysis of 4 representatives of the CaMK group and a MAP kinase confirms features that may be exploited in inhibitor design. Indeed, screening <it>Cp</it>CDPK1 against a library of kinase inhibitors yielded a set of the pyrazolopyrimidine derivatives (PP1-derivatives) with IC₅₀values of < 10 nM. The binding of a PP1-derivative is further described by an inhibitor-bound crystal structure of <it>Cp</it>CDPK1. In addition, structural analysis of <it>Cp</it>CDPK4 identified an unprecedented Zn-finger within the CDPK kinase domain that may have implications for its regulation.</p> <p>Conclusions</p> <p>Identification and comparison of the <it>C. parvum </it>protein kinases against other parasitic kinases shows how orthologue- and family-based research can be used to facilitate characterization of promising drug targets and the search for new drugs.</p

Comparison of areal productivity of Nannochloropsis oceanica between Lab-Scale and Industrial-Scale raceway pond

The areal biomass productivities (g−1 m−2 day−1) of Nannochloropsis oceanica between different sizes of way ponds were compared. Sequential batch cultivation using 2-m2, 20-m2, and 200-m2 raceway ponds with an industrial scale 4000-m2 raceway as the main culture was conducted in summer and autumn during 2017 at Whyalla, Australia. Areal productivities of sequential batch cultivation during the same culture period were 8.4 g ± 0.9 g−1 m−1 day−1 in the 2-m2 ponds, 9.3 g−1 m−1 day−1 in the 20-m2 ponds, and 8.0 g−1 m−1 day−1 in the 200-m2 ponds respectively. In parallel with the operation of the main 4000-m2 pond, some smaller scale ponds of 2, 20, and 200 m2 were operated at the same site under the same conditions. Areal productivity data of dry biomass of Nannochloropsis oceanica in each pond are very similar between industrial 4000-m2 pond and other smaller ponds. In this work, the authors demonstrate that using the growth rate and productivities of Nannochloropsis from smaller scale open ponds with the same depth is valid to estimate for large-scale ponds in excess of 4000 m2