This basic science research will lay the necessary foundation for future novel antimicrobial drug design efforts. Opine metallophores are recently identified novel metal acquisition small molecules made by diverse bacterial pathogens: Staphylococcus aureus. Pseudomonas aeruginosa. and Yersinia pestis. The operons for biosynthesis. export and re-uptake have only been reported in the last two years. and yet these systems have already been shown to be linked to pathogenesis in mouse models for bacteremia. lung infections and burn wound infections.

Basic Research

Cytokine storm or macrophage activation syndrome (MAS; (1)) leads to secondary haemophagocytic lymphohistiocytosis (sHLH) and a deadly sepsis-like multi-organ failure in severe viral infections (2.3). including COVID-19 (4.5). Currently there are no established safe and effective therapies against MAS (5.6). It is accepted that an improper interplay between pro- inflammatory (M1) and anti-inflammatory (M2) macrophages (7) is. in part. responsible for MAS. M1s are activated early during infection and secrete the ???storm??? of cytokines leading to hyper inflammation (8). Then.

This research project will seek to answer if the allosteric site in one subunit regulates the active site in the same subunit. a result that will simplify mechanistic interpretation of structural changes. Detailed understanding of the molecular mechanisms of hL-PYK will facilitate future drug designs to activate (or prevent inhibition of) this enzyme to reduced hepatic glucose secretion and counteract hyperglycemia.In both type 1 and type 2 diabetes. hepatic secretion of glucose is a primary contributor to hyperglycemia. In turn.

Basic Research

This research project will compare the strains we generate with those we purify from AD and AD related neurodegenerative disorders such as progressive supranuclear palsy. If we are successful in identifying an artificial disease-relevant strain. we will continue our screening efforts to identify disease-relevant tau aggregation inhibitors while simultaneously working toward building a library of tau aggregate strains for multiple neurodegenerative tauopathies. These efforts will not only greatly increase the probability of generating effective therapeutics.

The aim of this pilot study is to investigate adaptations to unpredictable environments in nocturnal galagos (Galagidae). Animal species may develop adaptive coping mechanisms to improve fitness in environments with unpredictable changes in climate extremes (e.g. El Ni??o). Gummivory - feeding on the gum and sap of woody plant species - is thought to be an adaptive strategy that may have evolved in response to these sudden unpredictable environmental changes. This research will be conducted on Bioko Island. Equatorial Guinea. Bioko is a biodiversity ???hotspot???

Basic Research

Basic Research

Since its discovery from the extracts of sweet wormwood (Artemisia annua) in 1979. the anti-malarial drug artemisinin (3) is now the key starting material in the synthesis of life-saving artemisinin-based combination therapies (ACT). Yet. beginning in 2009. mutations in the parasites PfKelch13 protein began conferring artemisinin resistance in the Greater Mekong Subregion (GMS) (Figure 1).Since then. artemisinin resistance has been spreading and some ACT treatment failure rates have reached 26% to 46% in 2015.