Thread by @shaharbrr

So so so so excited to share this!
This preprint summarizes my journey of trying to engineer the brain parasite Toxoplasma gondii to deliver therapeutic proteins into neurons, together with @OdedRechavi and @SheinerLab 1/n biorxiv.org/content/early/… #bioRxiv

You probably heard of Toxoplasma because of the way it cycles between cats and their prey. However, Toxoplasma also infects people. 2/n

Toxoplasmosis can be dangerous in people with weakened immune systems, but in most people infections are asymptomatic, and aren’t even noticed. In fact, it is estimated that a third of the human population are chronically infected with Toxoplasma. 3/n

A special thing about Toxoplasma is that when it infects humans, it knows how to migrate into our central nervous system, bypass the blood-brain-barrier and persist in the brain for a very long time. 4/n

Another thing is its three specialized secretion systems, through which it can secrete proteins into the cells of the host it infects. 5/n

These important skills were developed as an adaptation to Toxoplasma’s niche as a chronic intracellular parasite, through the co-evolution of Toxoplasma and its hosts. 6/n

We noticed that these special skills of Toxoplasma answer the exact problems that hinder the delivery of macromolecules to the brain. We therefore wondered if these mechanisms can be harnessed for the delivery of therapeutic protein to the CNS. 7/n

This wasn’t a straightforward journey though, because Toxoplasma is quite a weird organism (an apicomplexan protist), and its not fully understood what makes some protein secreted and some not. 8/n

So we tested different secretion systems and different protein configurations until finally we found some that were secreted. Through these attempts, we also managed to show some cool things about the mechanism by which Toxoplasma secrets proteins to the host. 9/n

Focusing on MeCP2, the protein missing in Rett syndrome, we show that our parasites can deliver MeCP2 to neurons, and we can even see it binding DNA in their nucleus the same way normal MeCP2 does! 10/n

This is important for showing that the protein Toxoplasma secrets is functional and could potentially replace the missing MeCP2 in Rett syndrome neurons. 11/n

This is the tip of the iceberg, and there are many things that must be done until Toxoplasma parasites can be used to deliver therapy in people. 12/n

But we believe that by harnessing what was developed and perfected by this parasite for its own needs, we can provide a new method for delivery of therapeutics to the brain, which overcomes many of the hard challenges faced by current ‘man-made’ drug delivery systems. 13/n

This project was a huge part of my life for the past 5 years, and it taught me a lot, about science, about myself, and about what excites me the most in science. Looking forward to hear your thoughts and comments! 14/n

Thanks to my mentors @OdedRechavi and @SheinerLab, everyone in both labs and especially Karoliina, our collaborator Stuart Cobb and everyone who helped along the way. Living between Tel Aviv and Glasgow wasn't easy, but being surrounded by friends made the whole difference