blankedoutmap.png
DMSO_1500X_0009.jpg
D10 +48hr.jpg
blankedoutmap.png

Introduction


how do pathogens know where they are?

SCROLL DOWN

Introduction


how do pathogens know where they are?

 

We are interested in the interaction of the apicomplexan parasites such as Toxoplasma and Plasmodium with their respective host cells. Both are obligate intracellular parasites, that display distinct survival and developmental phenotypes in certain environments. For example, the asexual replication phenotype is only expressed inside the protective host-cell environment following invasion of that cell. Replication does not take place outside of a host-cell.

How do these pathogens know where they are?

How do they know if there are intracellular or extracellular?

What are the cellular events or signals that form the molecular basis for this environmental phenotypic plasticity?

The core chemical biology and molecular parasitology skill-sets present within our lab puts us in a unique position to answer these questions. We combine chemistry, biochemistry, molecular and cell biology tools, chemical genetic and chemoproteomic techniques to interrogate the integrated biology of host-pathogen interactions.

 
DMSO_1500X_0009.jpg

Toxoplasma


Toxoplasma

Toxoplasma gondii (T. gondii) is a single-cell parasite, and the most successful parasite on the planet, infecting up to a third of the world’s human population. Inside a host T. gondii develops within a host-cell. How the parasite detects and interprets biological information (signals) within this cell is poorly understood. These signals can be transmitted by Reactive Oxygen Species (ROS) such as hydrogen peroxide. ROS are encountered by T. gondii during replication within a host cell, and when outside of this cell and visible to the host immune system. Though the parasite experiences ROS signals, how they are detected and how the parasite responds is not known and is one avenue of research we are pursuing.

Toxoplasma


Toxoplasma

Toxoplasma gondii (T. gondii) is a single-cell parasite, and the most successful parasite on the planet, infecting up to a third of the world’s human population. Inside a host T. gondii develops within a host-cell. How the parasite detects and interprets biological information (signals) within this cell is poorly understood. These signals can be transmitted by Reactive Oxygen Species (ROS) such as hydrogen peroxide. ROS are encountered by T. gondii during replication within a host cell, and when outside of this cell and visible to the host immune system. Though the parasite experiences ROS signals, how they are detected and how the parasite responds is not known and is one avenue of research we are pursuing.

D10 +48hr.jpg

Plasmodium


Plasmodium

An aspect of the host redox machinery yet to be studied in the context of intracellular pathogens is the recently discovered redox circadian rhythm (RCR). Though our understanding of the molecular basis for this oscillation remains incomplete, it is present in all domains of life and is independent of canonical transcription-factor clock machinery. Distinguishing the contribution of the redox rhythm from clock transcription factors to biological processes is challenging, but enucleated mature erythrocytes provide an ideal system for its study, where the RCR is present but canonical circadian clock components and structures are notably absent. Intracellular pathogens that infect erythrocytes (such as Plasmodium spp.) provide a unique opportunity to study the host-cell RCR within the context of a pathogenic infection and is a second major research interest of our lab.

Plasmodium


Plasmodium

An aspect of the host redox machinery yet to be studied in the context of intracellular pathogens is the recently discovered redox circadian rhythm (RCR). Though our understanding of the molecular basis for this oscillation remains incomplete, it is present in all domains of life and is independent of canonical transcription-factor clock machinery. Distinguishing the contribution of the redox rhythm from clock transcription factors to biological processes is challenging, but enucleated mature erythrocytes provide an ideal system for its study, where the RCR is present but canonical circadian clock components and structures are notably absent. Intracellular pathogens that infect erythrocytes (such as Plasmodium spp.) provide a unique opportunity to study the host-cell RCR within the context of a pathogenic infection and is a second major research interest of our lab.