Alexander Mühleip’s project will focus on understanding how the mitochondrion, the powerhouse of the cell, undergoes structural changes during the parasite's life cycle. These changes are crucial for the parasite's ability to transition between different stages of its complex lifecycle, which includes human and mosquito hosts. As the parasite moves through these stages, it rewires its metabolism and remodels its mitochondrion to adapt to the varying environments it encounters.
Understanding the fundamental biology governing this process may open up new avenues for controlling the spread of malaria and for future development of antimalarials. There were an estimated 249 million malaria cases worldwide in 2022, based on the WHO World malaria report 2023.
Mühleip’s research group will employ advanced techniques such as electron cryo-microscopy and cryo-tomography to resolve the molecular structures of the membrane protein complexes responsible for mitochondrial plasticity. By deciphering the roles of parasite-specific components in mitochondrial energy conversion, the team hopes to uncover the molecular basis of mitochondrial remodelling in Plasmodium falciparum.
“Targeting the mitochondrion has already been validated as a strategy for antimalarial drug treatments. By providing detailed insights into the unique structures of mitochondrial protein complexes in malaria parasites, we aim to contribute new insight that could inform the design of new antimalarial inhibitors.”, Mühleip describes his group’s work.
Mühleip’s group has previously studied the structure and function of mitochondrial membrane protein complexes involved in membrane bending. Their work has revealed that the energy-converting complexes in unicellular organisms, including human parasites, differ significantly from those in humans. These findings have offered new perspectives on how these complexes function and how they shape the bioenergetic membrane of the mitochondrion.
The ERC funding will allow Mühleip’s team to push the boundaries of our understanding of mitochondrial dynamics in malaria parasites and aim to use new insights into their unique biology to inform antimalarial drug development.
The ERC Starting Grants amount to €1.5 million per grant for a period of five years. The grant is intended for establishing a research group and launching independent research activities in Europe.