My research goal is to characterize and understanding how F-box proteins function in Toxoplasma gondii. Our knowledge about this class of proteins in the parasitology field is vastly unexplored. Therefore, completion of this goal will unveil novel molecular mechanisms that are present in T. gondii but absent in humans.
Toxoplasma gondii is an obligate intracellular parasite responsible for one of the most widespread parasite in the world. Luckily, most infected people are asymptomatic. However, in immune-compromised individuals, T. gondii causes serious and life-threatening disease. Additionally, T. gondii represents an ideal model system to study how other related pathogens like Plasmodium spp and Cryptosporidium spp cause disease.
Previous studies from the lab showed that a prolyl 4-hydroxylase modifies a proline in Skp1, which is a component of the Skp1/Cullin1/F-box protein/Rbx1 (SCF-type E3) ubiquitin ligase complex. This post-translational modification changes the Skp1 binding affinity for the F-box proteins 1 (FBXO1) specially at low oxygen levels. Because F-box proteins are substrate recruiting subunits of the (SCF)-type E3 ubiquitin ligase we hypothesize that T. gondii is able to rapidly change its proteome in response to oxygen levels by change the Skp1 affinity for different F-box proteins.
The results from this research may be exploited for the development of future chemotherapeutic approaches to combat the deadly diseases caused by Apicomplexa parasites.
Carlos Gustavo Baptista, PhD
955 Main Street, Suite 5260
Phone: (716) 645-6790