Dr Michael Lewis

Supervisor Details

Contact Details

Warwick Medical School, University of Warwick

Scientific Background

Research Interests

Kinetoplastid parasites comprise a diverse class of flagellated eukaryotic protozoa that diverged very early in the evolution of eukaryotes. This group includes three of the most important human protozoan pathogens: Trypanosoma cruzi, causative agent of American trypanosomiasis (Chagas disease); Trypanosoma brucei, which causes African trypanosomiasis (sleeping sickness); and species of the genus Leishmania which cause various clinical forms of leishmaniasis. As a result of sophisticated immune evasion strategies, kinetoplastids often cause long-term chronic infections. This can result in highly variable clinical outcomes between individual infected people, ranging from death and severe morbidity to milder forms and subclinical carrier states. The host, parasite and environmental factors that determine these heterogeneous outcomes are poorly understood. I aim to discover the mechanisms which determine host-parasite interaction dynamics during these infections and how these in turn shape tissue pathogenesis and organ dysfunction.

My main research focus is Trypanosoma cruzi biology and Chagas disease pathogenesis. There is a well-developed genetic engineering toolbox for T. cruzi, including bioluminescent:fluorescent fusion reporter genes and CRISPR-Cas9 systems for genome editing. This enables us to track the spatio-temporal dynamics of T. cruzi infections using in vitro, in vivo and ex vivo imaging models and to test hypotheses relating to parasite genetic factors by generating knockout, tagged and overexpression mutants. On the host side, we aim to use a variety of cutting-edge approaches to analyse immune responses, tissue damage and organ dysfunction, which can also be manipulated using genetic, chemical and immunomodulatory techniques. Integrating data on host, pathogen and pathology will help us to develop a more holistic understanding of the biological mechanisms involved in Chagas disease. We aim to use this knowledge to inform the development of more effective approaches to diagnosis and treatment.

Research Groups

Lewis Lab

Supervision Style

In three words or phrases: flexible, enthusiastic, student-centred.

Provision of Training

We will develop a personalised approach to your training, regularly reviewing the balance of technical supervision and independence.

Progression Monitoring and Management

We will meet on a roughly monthly basis to agree goals for your research and wider professional development, but we will discuss experimental methods and data on a daily to weekly basis. A high degree of self-motivation will help you to get the most out of your project.

Communication

I prefer to keep communications to within the working day. We will develop a personalised approach to modes of communicating with each other.

PhD Students can expect scheduled meetings with me:

In a group meeting

At least once per week

In year 1 of PhD study

At least once per week

In year 2 of PhD study

At least once per month

In year 3 of PhD study

At least once per month

These meetings will be face to face. I am usually contactable for an instant response 3 or 4 days a week.

Work Patterns

Certain tasks in my lab need to occur at set times, and students need to be able to commit to a rota/timetable shared with other members of the team.

Notice Period for Feedback

I need at least 2 weeks' notice to provide feedback on written work of up to 5000 words.

MIBTP Project Details

Current Projects (2025-26)

Primary supervisor for:

Understanding the role of the flagellum in Trypanosoma cruzi intracellular parasitism

See the PhD Opportunities section to see if this project is currently open for applications via MIBTP.

Please Note: The main page lists projects via BBSRC Research Theme(s) quoted and then relevant Topic(s).

Understanding the role of the flagellum in Trypanosoma cruzi intracellular parasitism

Secondary Supervisor(s): Dr Samuel Dean

University of Registration: University of Warwick

BBSRC Strategic Research Priority: Understanding the Rules of Life (Microbiology)

Project Outline

Parasitism, in which one species benefits at the expense of another species by living in or on it, is one of the most common modes of life. Eukaryotic parasites (protozoa and helminths) have complex life cycles that involve stages in more than one host species. They often alternate between vertebrates and invertebrates, requiring rapid adaptation to new environments. Parasites also have distinct morphological forms that occupy different niches within their hosts; typically, these are specialised for clonal replication, sexual reproduction or transmission. Sustaining this way of life requires two essential capabilities – motility and environmental sensing. In trypanosomes, both these functions are associated with a remarkable organelle, the flagellum.

Flagella are microtubule based cellular protrusions present across many eukaryotic lineages, including trypanosome parasites. Motile flagella ‘beat’ due to motility structures in the flagellar axoneme, whereas immotile flagella are thought to act as a cellular ‘antennae’. They have diverse functions in the life cycle, including cellular locomotion, environmental sensing, host-parasite and parasite-parasite communication. This organelle has been extensively studied in African trypanosomes and to some extent in the epimastigote (insect form) of the American trypanosome Trypanosoma cruzi (Tc), the causative agent of Chagas disease in humans. In African trypanosomes, the flagellum has long been acknowledged be essential for parasite infectivity and pathogenicity, and flagellar-driven motility has key roles in immune evasion. In Tc amastigotes, the proliferative forms that reside in the cytosol of infected host cells, the flagellum has been considered a functionally irrelevant, vestigial remnant. Recent recordings of amastigote flagellar beating inside infected cells, observation of contacts with host mitochondrial membranes and development of CRISPR-Cas9 editing tools for this parasite provide a timely opportunity for us to investigate the hypotheses that a) Tc in fact requires amastigote flagellar motility to survive inside host cells, and b) that this involves dynamic, flagellum-mediated interactions with diverse host cell organelles to monitor the host cell environment.

Objectives

Project objectives will be to:

Engineer a transgenic Tc parasite line that has a fluorescent flagellum membrane that enables this organelle to be tracked in space and time.

Delete genes predicted to have flagellum biology functions from the parasite genome and evaluate the phenotypic effects on motility and virulence through the intracellular Tc life cycle.

Analyse the spatio-temporal dynamics of interactions between the parasite’s flagellum and the host cell’s membrane-bound organelles and evaluate the impact of flagellum component deletions on these interactions.

The project will involve a range of methods, from molecular biology and CRISPR-Cas9 genome editing tools to advanced microscopy and host-parasite co-cultures within state-of-the-art BSL-3 containment laboratories.

References

Costa et al. Expanding the toolbox for Trypanosoma cruzi: A parasite line incorporating a bioluminescence-fluorescence dual reporter and streamlined CRISPR/Cas9 functionality for rapid in vivo localisation and phenotyping. PLoS Negl Trop Dis. 2018 Apr 2;12(4):e0006388. doi: 10.1371/journal.pntd.0006388. PMID: 29608569.

Won et al. The Intracellular Amastigote of Trypanosoma cruzi Maintains an Actively Beating Flagellum. mBio. 2023 Apr 25;14(2):e0355622. doi: 10.1128/mbio.03556-22. Epub 2023 Feb 22. PMID: 36840555.

Sáez Conde & Dean. Structure, function and druggability of the African trypanosome flagellum. J Cell Physiol. 2022 Jun;237(6):2654-2667. doi: 10.1002/jcp.30778. Epub 2022 May 26. PMID: 35616248.