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The Tewari Lab

Unravelling Malaria Parasite Cell Biology and Development

Malaria is an infectious disease that threatens 40% of total world’s population, the majority living in developing countries. There are ~500 million clinical cases and 1 million deaths per year, mostly of children. The disease is caused by an apicomplexan protozoan parasite of the genus Plasmodium that is transmitted by the bite of an infected female Anopheles mosquito. The parasite develops and multiplies within the liver of the human host and then infects and multiplies within red blood cells. This asexual blood stage is responsible for the pathology of the disease. The control of the disease is hampered by the lack of an effective vaccine and the ever increasing resistance to antiparasite drugs and of mosquitoes to insecticides. Control strategies are further limited by the complex life cycle of the malaria parasite that has developmental stages within the liver and blood of the human host and in the gut and salivary glands of the mosquito. To develop rational and effective intervention strategies, understanding the biology of parasite development and the signalling processes that control it are crucial.

Our research is mainly aimed to understand the molecular pathways that are involved in malaria parasite development and differentiation, cell division, and parasite interactions with both mammalian and vector host. We use molecular, genetic, cell biology, biochemistry, proteomics and reverse genetics approaches to study the function of regulatory protein families like kinases, phosphatases, cell division proteins and armadillo repeat proteins in malaria parasite biology. The aim is to identify the best drug and vaccine targets and along the way understand basic parasite cell and developmental biology. For all these studies we use rodent malaria model Plasmodium berghei that is easily amenable to reverse genetic studies and whole life cycle of parasite can be studied both in mammalian host and vector mosquito.

Zygote retorts showing apical GFP expression
Sporozoite with surface and apical GFP expression
Schizont showing surface GFP expression
Female zygote with nuclear GFP expression
Ookinete showing apical GFP expression
Oocyst with sporozoites

Malaria Kinases Phosphatases Signalling Development Cell Biology Gametocyte Ookinete Sporozoite Merozoite Apical Drug discovery Armadillo repeat proteins Invasion

Recent News

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Published in Press Releases, the 05/07/2017

Science initiated in Nottingham has helped to form the foundation for the latest breakthrough in the global fight against malaria.

Researchers in the University of Nottingham’s School of Life Sciences were responsible for the identification of the molecular switches that control the three key stages of the malaria parasite’s life cycle – work which has underpinned a new discovery about the way in which the growth of the parasite is controlled.

Now, a team of international scientists led by Portuguese academics has discovered that one of the proteins identified by the Nottingham experts plays a vital role in modulating the parasite’s rate of replication by sensing the nutritional status of its host.

Published in General, the 26/05/2017

Our first Midlands Cell Cycle and Cytoskeleton Club meeting will take place on 11th July 2017.
This is not a open public event.

Published in General, the 01/04/2017

Anthonius Eze has been successful to get Commonwealth Academic Fellowship to work on Aurora kinases in malaria parasites. Many congratulations.

Published in Opportunities, the 20/03/2017

The UK has been a world leader in medical imaging since the 1960s, including the groundbreaking development of MRI led by Sir Peter Mansfield in Nottingham, enabling major advances in our knowledge about in vivo functional anatomy of whole organs and their substructures, especially the brain and as a non-invasive diagnostic tool.

Advanced imaging modalities have been crucial aids to our fundamental scientific understanding of cellular and molecular processes underlying biological function and disease. Research projects and training in this theme will demonstrate that advances in knowledge are not just a matter of having access to state-of-the-art technologies, but require an interdisciplinary combination of technological expertise and biological/medical knowledge to formulate answerable questions and to interpret the results.

Published in Opportunities, the 20/02/2017

Applications are invited from highly motivated and enthusiastic candidates for an MRC-funded PhD studentship aimed at identifying new therapeutic approaches to malaria.

Plasmodium, the causative agent of malaria, leads to 200 million cases and kills more than half a million people annually. Measures to control exposure to the mosquito vector have met with limited success and resistance to current drugs is emerging rapidly. This project will explore the roles of four NEK kinases expressed by the parasite and test their potential as novel therapeutic targets for malaria.

The objectives are to:

  • define the subcellular localisation of NEKs during the parasite life cycle using advanced imaging techniques;
  • use tagged NEK transgenic lines and mass spectrometry to identify interacting partners; and
  • study the function of NEKs in parasite proliferation using conditional gene targeting in cell and animal models.

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