Lab Members

Moritz Treeck | Group Leader 

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Moritz Treeck

Broadly speaking, I am really interested to understand how host- pathogen interaction works on multiple levels. The parasites we work with, Plasmodium falciparum and Toxoplasma gondii both evolved to excel at infecting and modifying host cells and a huge proportion of the proteins important for these processes are poorly characterized. I very much enjoy working with a team of talented and enthusiastic individuals in the lab to unravel the complexity of host pathogen interaction.  Often this involves the development of new methods to overcome challenges. The scientific environment of the Francis Crick Institute enables us to use the latest technology developments to pursue these goals, often in collaboration with research groups from around the world.

 

Biography: I was born in the rainy city of Hamburg in northern Germany and I almost ended up as a lawyer. I prepared two applications, one for law and one for biology, and inserted one application blind-folded into the post-box. Law was still in my hands and I am thankful for this until the very day. Throughout my academic career I was interested in parasites and I have tried to attract as many as possible during my travels to Central America and South-East Asia. However, it was not until I met my future PhD advisor Tim Gilberger during a semester in Melbourne, Australia, where I got hooked working with malaria. I spent my PhD thesis at the Bernhard-Nocht Institute for Tropical Medicine in Hamburg, Germany, studying protein trafficking and invasion of red blood cells by the malaria parasite. After that I  moved to John Boothroyd’s lab in Stanford, California to learn as much as I could about another really interesting parasite, Toxoplasma. After 4 years I returned to Europe to join the Francis Crick institute, which offered an outstanding research environment in a vibrant city.

Heledd Davies

Heledd Davies | Post-doctoral Researcher

What is the function of post-translational modification in host cell remodelling by Plasmodium falciparum? 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 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. 

Davies, Belda et al.

An exported kinase family mediates species specific erythrocyte remodelling and virulence in human malaria

Nature Microbiology 2020

Malgorzata Broncel
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Goska (Malgorzata) Broncel | Post-doctoral Researcher

How can post-translational modifications and protein-protein interactions at the host-parasite interface be monitored using mass spectrometry? Quantitative shotgun proteomics is a key method to profile signalling pathways controlled by kinases and phosphatases and to identify their substrates. However, by nature it is not highly reproducible between replicates and as such not the ideal strategy to analyse already known signalling events at high temporal resolution with high reproducibility. I am interested in establishing targeted proteomics methods to achieve highly reproducible stoichiometric measurements of phosphorylation events as well as in application of chemical biology and highly multiplexed mass spectrometry workflows for studying host-pathogen interactions.

Goska obtained her PhD in the lab of Christian Hackenberger at Free University Berlin working on post-translational modifications and amyloid formation. She then moved as Marie Curie fellow to Ed Tate's lab at Imperial College London where she developed chemical probes to investigate post-translational modifications using mass spectrometry.

Francesca Torelli

Francesca Torelli | Post-doctoral Researcher

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What are the common and specific tools different Toxoplasma strains use to succeed in infection? Toxoplasma secretes a large number of proteins that mediate adhesion and invasion, establishment and defence of the parasitophorous vacuole, and influence various host cell pathways. However, most of these secreted proteins have unknown functions. I will be using our arrayed CRISPR library with both in vitro and in vivo selection methods to identify which of those proteins is important for Toxoplasma's success to establish an infection. Furthermore, by performing the screen on strains that differ in virulence, I will identify which of these virulence factors are generic and which are strain-specific. My position as post-doctoral fellow is currently funded by German Research Foundation (DFG).

 

Francesca completed her PhD in the Seeber lab at the Robert Koch Institute in Berlin, working on the resistance mechanisms of wild rodents to Toxoplasma infection. In future work she aims to explore tolerance mechanisms of parasites to host immune responses.

Francesca Torelli Figure 2

Francesca Torelli

Identification and characterisation of novel Toxoplasma gondii virulence factors in macrophages using tailored CRISPR screens in vivo

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Stephanie Nofal

Stephanie Nofal | Post-doctoral Researcher

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How does Toxoplasma integrate different signalling pathways to trigger egress? 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 egress from the host cell. I am currently investigating how specific CDPK3-dependent phosphorylation events regulate host cell egress. 

Stephanie completed her PhD in David Baker’s lab at the London School of Hygiene & Tropical Medicine, where she worked on cyclic nucleotide signalling and molecular motor function in the malaria parasite. 

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Stephanie Nofal

Signalling pathways in Toxoplasma gondii

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Jill Dalimot | Post-doctoral Researcher

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Anemia is a major complication during severe human malaria, leading to the destruction of up to 1 uninfected red blood cells for every infected red cell. This process may be mediated in trans, by parasite exported proteins, but the effectors and the mechanism by which this occurs is largely not known. Jill is interested in the function of FIKK kinases on the surface translocation and potential export or secretion of parasite proteins associated with pathology, such as rifins and stevors.

Jill performed her doctoral studies in the Institute Sanguin in the with Robin van Bruggen, investigating the interaction of malaria infected (and uninfected) red cells with the immune system of the host.

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Jill Dalimot

 

 

Hemolyzed uninfected RBCs

(stained green)

in a cell culture containing

infected red blood cells

(bright blue stain)

Hugo Belda

Hugo Belda | Postdoc

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What is the function of post-translational modification in host cell remodelling by Plasmodium falciparum? 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 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. 

Davies, Belda et al.

An exported kinase family mediates species specific erythrocyte remodelling and virulence in human malaria

Nature Microbiology 2020

Simon Butterworth

Simon Butterworth | PhD Student

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How do Toxoplasma effector proteins reprogram the host cell? Toxoplasma secretes a large number of effector proteins into its host cell which inhibit immune responses to the parasite and reprogram host transcription, but how these effectors work in the context of different parasite strains and host cell types is not well understood. I am using our arrayed CRISPR library to design a single-cell RNA-sequencing screen to identify and characterise effector proteins that influence host reprogramming across cell types and parasite strains.

Simon Butterworth

Single cell transcriptomes of Toxoplasma gondii infected human fibroblasts

Eloise Lockyer

Eloise Lockyer | PhD Student

How does Toxoplasma disarm the human innate immune response? Humans are ‘accidental’ intermediate hosts for Toxoplasma (unless eaten by a lion). Yet, given the widespread human seroprevalence and incidence of toxoplasmosis it is clear Toxoplasma can evade elimination by the human immune system. Mouse models are commonly used to study Toxoplasma infection in vivo, but the critical mediators of cell-autonomous immunity in mice are absent or altered in human cells. Some of the protein effectors that Toxoplasma secretes to disarm mouse innate immunity have been well characterised, but if and how these effectors operate in human cells is less well studied. I am using our arrayed CRISPR library to identify the key complement of effectors that are essential to Toxoplasma virulence in both mouse and human hosts.

Eloise Lockyer

Human macrophages (magenta) infected with Toxopasma gondii (green)

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David Jones

David Jones | PhD Student

David is interested in how the parasite Plasmodium falciparum responds and reacts to conditions met in a human host. While we can culture P. falciparum efficiently in human red blood cells, we miss the host environment and predict that the important function of many genes cannot be uncovered under standard cell culture conditions.

Alassane Mbengue

Alassane Mbengue | Visiting Scientist

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Alassane is a Crick African Network Fellow from the West African Centre for Cell Biology and Infectious Pathogens (WACCBIP), University of Ghana, and the Institut Pasteur de Dakar, Senegal. Drug-resistant strains of Plasmodium typically emerge from South-East Asia, however the major burden of malaria illness and mortality is in Sub-Saharan Africa. Mutations towards drugs resistance in Africa is therefore a major concern. In our lab Alassane will make use of the genetic tools we have developed for Plasmodium and the Crick's Advanced Sequencing facility to study the emergence of mutations leading to drug resistance in wild isolates of Plasmodium from West Africa.

Mbengue et al.

A molecular mechanism of artemisinin resistance in Plasmodium falciparum malaria

Nature 2015

Emmanuel Amlabu

Emmanuel Amlabu | Visiting Scientist

Emmanuel is a Crick African Network Fellow from the West African Centre for Cell Biology and Infectious Pathogens (WACCBIP), University of Ghana. He also holds a Faculty appointment at the Department of Biochemistry, Kogi State University, Anyigba, Nigeria. He is interested in understanding the functional roles of novel Plasmodium falciparum proteins during merozoite invasion and egress, with the hope of developing new intervention strategies against malaria. Emmanuel will be employing genetic tools, proteomics and imaging approaches to address his CAN project research questions while at the Francis Crick Institute

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Emmanuel Amlabu

Immunofluorescence microscopy image of Plasmodium falciparum schizont stage

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Omar Janha | Visiting Scientist

Omar is a Crick African Network Fellow from the MRC Centre at The Gambia. He is interested in identifying protein kinases as targets for transmission blocking drugs against malaria.
 

Protein kinases are key signal transducers of cellular processes in various stages of the Plasmodium life cycle including important roles in gametocyte commitment and development. Because of the importance of PKs in sexual commitment and gametocytes development, I am particularly interested in identifying suitable PKs to investigate as targets offering transmission blocking to stop the continuous spread of malaria in the wake and spread of parasites resistant to front-line antimalarial drugs including artemisinin as used in artemisinin combination therapy.

 

Omar completed his PhD from Prof Andrew Tobin’s malaria group in Glasgow University (formerly University of Leicester) in January 2019 working on validating P. falciparum CLK3 as a target offering cure, prophylaxis and transmission blocking for malaria where he developed keen interest in protein kinases