Postdocs

 

We are always interested in highly motivated postdocs to join the lab. Position available will be advertised here and on the Crick Institute homepage. We do welcome people who would like to join on their own funding and I will help to write these. However a very competetive track-record is essential for this. If interested please send a short CV and motivation letter.

Marta Tiburcio: Which kinases of the malaria parasite are key to virulence and transmission?
 

Among the major problems in eradicating malaria are 1) the ability of the parasite to switch its major antigens (the var genes), thereby constantly escaping the human immune response and 2) the efficient transmission of parasite sexual stages via the mosquito.  Both processes are regulated and there is indication that phosphorylation plays an important role. However, the kinases and signaling pathways involved have not been identified. I am trying to identify the regulators of these processes and develop tools to describe their function.

 

Marta did her PhD thesis as a joint PhD student in the laboratories of Pietro Alanao and Robert Sauerwein working on the transmission of the malaria parasite.

 

 

 

Joanna Young: What is the function of posttranslational modifications in the interplay between Toxoplasma gondii and its host cell?

 

The Toxoplasma parasite lives within a vacuole in a nucleated host cell. We have identified a large number of parasite proteins secreted into the host cell that are subject to substantial phosphorylation. I am trying to understand the function of these proteins, how post-translational modification adds to their function and most importantly, who are the regulators of these proteins (they could be parasite secreted kinases, but also host kinases).

 

Joanna obtained her PhD in the laboratory of Gad Frankel working on bacterial effector proteins injected into the host-cell.

Heledd Davies: What is the function of post-translational modification in supporting P. falciparum’s whole-sale take over of a red blood cell?
 

​P. falciparum exports a large number of proteins out into its host red blood cell. These proteins drive the transformation of red blood cells from oxygen-transporting cells with no nucleus and little of a typical cell’s internal machinery into a parasite-production facility that causes all of malaria’s most severe symptoms.  We and others have found that many of these exported proteins are phosphorylated, but the kinases responsible are not currently known and—most importantly—the functional consequences are a mystery. I am using quantitative phoshoproteomic methods and at the same time am developing new genetic tools to try and figure out how P. falciparum uses post-translational modification to take over red blood cells and cause disease. 

 

Heledd obtained her PhD at University College London in Andrew Osborne's lab. She has worked on protein trafficking and the function of peptide repeats in proteins the malaria parasite exports into the host cell. 

Mat

Malgorzata (a.k.a. Goska) Broncel: How can signalling events in host-pathogen interaction be monitored at high resolution and specificity using quantitative proteomics?
 

​Quantitative shotgun proteomics is a key method to identify signalling pathways controlled by kinases and phosphatases alike. However, by nature it is not highly reproducible between replicates and as such not the ideal strategy to identify already known signalling events at high temporal resolution with high reproducibility. Goska is interested in establishing targeted protemics methods to A) achieve highly reproducible coverage of key signaling events and B) to allow stochiometric measurements of phosphorylation events. This is especially complicated in host-pathogen interactions where two eukaryotic proteomes are contained within the same sample.

 

Goska has obtained her PhD in the lab of Christian Hackenberger working on post-translational modifications and amyloid formation and then moved as a Marie Curie postdoc to Ed Tate's lab where she continued to develop chemical probes to investigate post-translational modifications using mass-spectrometry.

Malgorzata (a.k.a. Goska) Broncel: How can signalling events in host-pathogen interaction be monitored at high resolution and specificity using quantitative proteomics?
 

​Quantitative shotgun proteomics is a key method to identify signalling pathways controlled by kinases and phosphatases alike. However, by nature it is not highly reproducible between replicates and as such not the ideal strategy to identify already known signalling events at high temporal resolution with high reproducibility. Goska is interested in establishing targeted protemics methods to A) achieve highly reproducible coverage of key signaling events and B) to allow stochiometric measurements of phosphorylation events. This is especially complicated in host-pathogen interactions where two eukaryotic proteomes are contained within the same sample.

 

Goska has obtained her PhD in the lab of Christian Hackenberger working on post-translational modifications and amyloid formation and then moved as a Marie Curie postdoc to Ed Tate's lab where she continued to develop chemical probes to investigate post-translational modifications using mass-spectrometry.

Francesca Torelli: How does Toxoplasma achieve tolerance?

The intracellular parasite Toxoplasma gondii resides and replicates within specifically formed vacuoles inside the host cell. To establish and to protect this unique niche from the host immune response, Toxoplasma secrets a large number of proteins that mediate adhesion and invasion, establishment of the parasitophorous vacuole and, most interestingly, influence various host cell pathways. We developed a CRISPR based library of Toxoplasma proteins that Francesca currently uses in combination with in vitro and in vivo selection methods to identify those proteins important for Toxoplasma virulence and maybe more interesting, how it achieves tolerance.

 

Before joining my team, Francesca was working in Berlin on the host cell side of Toxoplasma virulence in Frank Seeber's lab.

Caia Dominicus: How does Toxoplasma integrate different signalling pathways?

 

As other organisms, Toxoplasma uses several signalling molecules and pathways to control growth, stage conversion and dissemination.  It has recently been shown that the Toxoplasma plant-like kinase CDPK3 plays a key role in rapid parasite exit from the host cell, but also that the kinase likely has a broader function. I am interested in teasing apart the different functions and the effector proteins involved in various phenotypes.

Caia has obtained her PhD (almost there) from the University of Cambridge in the lab of Stefan Marciniak at the Cambridge Institute for Medical Research. There Caia worked on eIF2a phosphorylation during developmental processes.