How WEHI Scientists Are Helping Defeat Malaria: From Fundamental Discovery to New Treatments

⏱ In 30 Seconds

✓ Malaria remains a major global health threat because parasites and mosquitoes continue to evolve resistance to existing control measures.
✓ For more than three decades, WEHI scientists have studied how malaria parasites invade, survive and reproduce inside human cells.
✓ These fundamental discoveries have revealed new biological vulnerabilities that can guide the development of medicines and vaccines.
✓ One result of this long research journey is MK-7602, a first-in-class experimental antimalarial drug that has progressed into human clinical trials.

Why Malaria Still Matters

Malaria has been one of humanity’s deadliest infectious diseases for thousands of years.

Although remarkable progress has been made over the past two decades, the disease still causes hundreds of thousands of deaths each year, with young children in sub-Saharan Africa carrying the greatest burden.

Drug-resistant parasites, insecticide-resistant mosquitoes and the parasite’s remarkably complex life cycle continue to challenge scientists around the world.

These challenges mean that new treatments cannot rely only on improving medicines that already exist. Scientists must also uncover entirely new biological vulnerabilities within the parasite itself.

For decades, researchers at the Walter and Eliza Hall Institute of Medical Research (WEHI) in Melbourne have contributed to this global effort by asking one fundamental question: How does the malaria parasite survive inside the human body?

Understanding the Malaria Parasite

Malaria is caused by Plasmodium parasites, which are transmitted through the bite of infected Anopheles mosquitoes.

After entering the human body, the parasites first travel to the liver, where they infect liver cells and multiply.

They then enter the bloodstream and invade red blood cells. Inside these cells, the parasites grow, reproduce and eventually rupture their host cells before infecting new ones.

This repeating blood-stage cycle causes many of the characteristic symptoms of malaria, including fever and anaemia, and can lead to life-threatening complications.

Because the blood stage causes most clinical disease, understanding how parasites invade, remodel and survive inside red blood cells has become one of the central goals of malaria research.

WEHI’s Contribution to Malaria Research

For more than three decades, WEHI scientists have combined molecular biology, genetics, structural biology, immunology and drug discovery to investigate malaria at the cellular and molecular levels.

Rather than focusing only on producing new drugs, researchers have sought to answer fundamental biological questions.

How does the parasite recognise and enter a red blood cell?

How does it remodel the cell after invasion?

How does it obtain nutrients, avoid immune detection, reproduce and escape before infecting new cells?

Answering these questions has revealed proteins and biological pathways that the parasite depends on for survival.

Some of these molecules can potentially become drug targets. Others may provide clues for developing vaccines that prevent infection or reduce transmission.

Fundamental research can reveal biological vulnerabilities long before their eventual clinical use becomes clear. The same principle can be seen in Donald Metcalf’s discovery of G-CSF and its later clinical impact.

Why Red Blood Cell Invasion Matters

The malaria parasite cannot cause sustained blood-stage infection unless it can repeatedly invade new red blood cells.

This invasion process happens rapidly and requires a carefully coordinated sequence of interactions between parasite proteins and molecules on the surface of the host cell.

Researchers have worked to identify the molecular machinery involved in this process and determine which parasite proteins are essential.

If one of these critical steps can be interrupted, the parasite may be unable to continue its life cycle.

Understanding invasion therefore provides two major opportunities: blocking infection with vaccines and disrupting essential parasite functions with medicines.

Finding Vulnerabilities in a Complex Parasite

Malaria parasites are exceptionally difficult organisms to study because they move between mosquitoes and humans and pass through several distinct developmental stages.

At each stage, they express different proteins and interact with different host cells. A molecule that is essential during red blood cell invasion may be less important during liver infection or mosquito transmission.

This complexity means that researchers must examine the parasite across its life cycle rather than focusing on a single moment of infection.

Advances in genome sequencing, gene editing, structural biology and high-resolution imaging are providing an increasingly precise map of the parasite’s essential machinery and the points at which it may be disrupted.

From Fundamental Discovery to MK-7602

The road to MK-7602 did not begin with medicinal chemistry.

Years earlier, WEHI scientists were uncovering how malaria parasites invade red blood cells, evade host immune defences and carry out the molecular processes required for survival.

With each discovery, researchers gained a deeper understanding of the parasite’s most vulnerable biological functions.

Over time, these findings revealed new opportunities for therapeutic intervention and identified parasite proteins that could serve as future drug or vaccine targets.

Building on this knowledge, WEHI researchers and medicinal chemists collaborated with scientists at MSD to develop MK-7602.

MK-7602 is a first-in-class experimental drug designed to inhibit two essential malaria parasite enzymes: plasmepsin IX and plasmepsin X.

These enzymes are involved in critical processes associated with parasite invasion, development and transmission.

By targeting both enzymes simultaneously, researchers hope to create a treatment with a new mechanism of action and a higher barrier to the development of resistance.

The programme has now progressed into human clinical trials, marking an important transition from fundamental parasite biology to early clinical medicine.

Why Basic Research Takes Time

The development of a medicine such as MK-7602 illustrates why major biomedical breakthroughs often require decades.

Before a drug can be designed, researchers must understand enough about the disease-causing organism to identify a suitable target.

Scientists must then determine whether blocking that target is likely to harm the parasite, whether a chemical compound can reach it and whether the compound can be made sufficiently selective and safe.

Promising molecules must pass through repeated rounds of testing, optimisation and preclinical assessment in carefully selected experimental models before they can enter a human clinical trial.

Many candidates fail along the way.

The drugs that eventually reach clinical development are therefore built on a much larger body of research. A similar long translation from basic biology to therapy shaped the Australian discovery story behind Venetoclax, including experiments that initially appeared far removed from patient treatment.

A Personal Note

As a researcher, I think this is one of the hardest things to explain about fundamental research.

A project can look very far removed from medicine while it is being done. Scientists may spend years studying a protein, a pathway or a cellular process without knowing whether that work will ever lead to a treatment.

There is an old saying from The Art of War: “Know your enemy and know yourself, and you need not fear the result of a hundred battles.”

I think there is something in that for science too. Knowing the enemy means understanding the parasite. But knowing ourselves also means recognising the limits of what we know — and being willing to say, “We don’t know yet.”

To me, that is part of good science. Before we can defeat the parasite, we first have to understand it, and that begins with being honest about what we still do not understand. The medicine may come much later; the knowledge has to come first.

Why This Discovery Still Matters

The fight against malaria is far from over. As parasites continue to evolve resistance, researchers must keep identifying biological vulnerabilities that can be translated into new treatments.

WEHI’s malaria research shows why this process begins with a deep understanding of parasite biology. A useful drug target cannot simply be guessed; scientists first have to discover which parasite proteins are essential, how they function and whether interfering with them is likely to stop infection.

MK-7602 provides one concrete example of how decades of fundamental discovery can eventually produce a completely new therapeutic strategy.

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