WEHI researchers are tracking the healthcare experiences of culturally diverse men with prostate cancer for the first time, in a landmark project aimed at closing the healthcare gap in patient care.

The project will assess the lived experiences of hundreds of patients from culturally and linguistically diverse (CALD) backgrounds to better understand how cultural barriers impact their care and outcomes.

The study, funded through a Movember grant, is the first in Australia to collect such comprehensive data about the healthcare journeys of CALD patients in hopes of creating a more equitable healthcare system.

·      Researchers will monitor the healthcare experiences of CALD men with prostate cancer for the first time, in a landmark project aimed at closing the healthcare gap in cancer care.

·      The project will look at how cultural and language barriers can negatively impact access to health care and potentially lead to poorer health outcomes in this cohort of patients.

·      The findings will help inform health policies that could make strides towards providing inclusive care for all patients in Australia.

Prostate cancer is the most common cancer in Australian men, with 1-in-5 males diagnosed with the disease.

While the reported incidence of prostate cancer among immigrant men is lower, this is believed to be due to lower screening rates, likely underpinned by language and cultural barriers.

To address this challenge, WEHI researchers launched PROCAP – a project aiming to better understand and address the barriers facing CALD men with prostate cancer.

Clinician researcher Associate Professor Ben Tran has personal insight into the issue, with his Vietnamese grandfather dying of metastatic prostate cancer in 2005.

Instead of being prescribed a standard hormone therapy that reduces testosterone levels, his grandfather was advised to have both testicles surgically removed, causing significant distress to him and his family.

Assoc Prof Tran says language barriers and subsequent difficulties navigating the Australian healthcare system are likely to have impacted the care that was provided and believes stories like this are just the tip of the iceberg.

“Australia is one of the most multicultural countries in the world, with culturally and linguistically diverse individuals representing a third of the population,” Assoc Prof Tran, also a co-lead on PROCAP, said. 

“But they can often face greater challenges when accessing healthcare due to various language and cultural factors.

“Anecdotally, we also hear that patients who speak a language other than English report lower satisfaction ratings following healthcare experiences, have higher rates of adverse events from healthcare and increased rates of preventable hospitalisations. But there’s currently no data to support these anecdotal observations.

“We hope our study will generate the data needed to change this narrative and help efforts to advocate for minority groups that historically don’t have great advocacy in the healthcare system.”

PROCAP will enrol 300 CALD patients with advanced prostate cancer over the next two years, with participants completing a series of questionnaires that aim to capture their healthcare experiences and quality of life at specific time points along their treatment course.

WEHI researcher and project co-lead, Dr Arsha Anton, said the patient responses will provide insight into the treatment journeys of minority groups who continue to be underrepresented in Australia’s healthcare system.

“Clinical trials often don't include enough patients from culturally diverse populations, so very little is known about their experiences with prostate cancer, ability to cope with certain treatments and patient-reported outcomes,” Dr Anton said.

“The aim of PROCAP is to compare the quality of life and healthcare experiences of CALD patients with other Australians to identify the areas in need of extra support.

“Having access to this real-world data would help us understand how cancer treatments and consultations should be tailored for these individuals, to ensure they feel safe and confident within our healthcare system.

“We want everyone in Australia to feel assured that they will always get the best healthcare locally available, irrespective of cultural background. This project is a huge step forward in bolstering that trust within multicultural communities.”

Researchers say PROCAP may also be used as a framework in other cancer types, to track the healthcare experiences of CALD women and their treatment experiences in the future.

Study participants will be selected through ePAD – a multinational registry that collates demographic, treatment and outcome data of patients with advanced prostate cancer.

The project, “PROCAP: Using Patient-Reported Outcome and Experience Measures to Identify and Overcome Disparities in CALD Patients with Advanced Prostate Cancer,” is supported with over $398,000 in funding from Movember’s Personalised Prostate Cancer Care Initiative.

Sarah Weller, Global Director of Prostate Cancer at Movember, said: “Movember’s committed to ensuring that every man has access to the best possible prostate cancer care.

“The PROCAP study is a critical step toward addressing the healthcare inequities faced by multicultural communities, ensuring that cultural and language barriers don’t stand in the way of better health outcomes.

“Through our Personalised Prostate Cancer Care Initiative, we are proud to be funding this groundbreaking research alongside five other global projects, bringing our total investment to $2.1 million.

“By supporting studies like PROCAP, we can drive real change in healthcare systems worldwide, ensuring that men receive care tailored to their unique needs and experiences.”

WEHI researchers are tracking the healthcare experiences of culturally diverse men with prostate cancer for the first time, in a landmark project aimed at closing the healthcare gap in patient care.The project will assess the lived experiences of hundreds of patients from culturally and linguistically diverse (CALD) backgrounds to better understand how cultural barriers impact their care and outcomes.The study, funded through a Movember grant, is the first in Australia to collect such comprehensive data about the healthcare journeys of CALD patients in hopes of creating a more equitable healthcare system.At a glance· Researchers will monitor the healthcare experiences of CALD men with prostate cancer for the first time, in a landmark project aimed at closing the healthcare gap in cancer care.· The project will look at how cultural and language barriers can negatively impact access to health care and potentially lead to poorer health outcomes in this cohort of patients.· The findings will help inform health policies that could make strides towards providing inclusive care for all patients in Australia.Prostate cancer is the most common cancer in Australian men, with 1-in-5 males diagnosed with the disease.While the reported incidence of prostate cancer among immigrant men is lower, this is believed to be due to lower screening rates, likely underpinned by language and cultural barriers.To address this challenge, WEHI researchers launched PROCAP – a project aiming to better understand and address the barriers facing CALD men with prostate cancer.Clinician researcher Associate Professor Ben Tran has personal insight into the issue, with his Vietnamese grandfather dying of metastatic prostate cancer in 2005.Instead of being prescribed a standard hormone therapy that reduces testosterone levels, his grandfather was advised to have both testicles surgically removed, causing significant distress to him and his family.Assoc Prof Tran says language barriers and subsequent difficulties navigating the Australian healthcare system are likely to have impacted the care that was provided and believes stories like this are just the tip of the iceberg.“Australia is one of the most multicultural countries in the world, with culturally and linguistically diverse individuals representing a third of the population,” Assoc Prof Tran, also a co-lead on PROCAP, said. “But they can often face greater challenges when accessing healthcare due to various language and cultural factors.“Anecdotally, we also hear that patients who speak a language other than English report lower satisfaction ratings following healthcare experiences, have higher rates of adverse events from healthcare and increased rates of preventable hospitalisations. But there’s currently no data to support these anecdotal observations.“We hope our study will generate the data needed to change this narrative and help efforts to advocate for minority groups that historically don’t have great advocacy in the healthcare system.”Unprecedented dataPROCAP will enrol 300 CALD patients with advanced prostate cancer over the next two years, with participants completing a series of questionnaires that aim to capture their healthcare experiences and quality of life at specific time points along their treatment course.WEHI researcher and project co-lead, Dr Arsha Anton, said the patient responses will provide insight into the treatment journeys of minority groups who continue to be underrepresented in Australia’s healthcare system.“Clinical trials often don't include enough patients from culturally diverse populations, so very little is known about their experiences with prostate cancer, ability to cope with certain treatments and patient-reported outcomes,” Dr Anton said.“The aim of PROCAP is to compare the quality of life and healthcare experiences of CALD patients with other Australians to identify the areas in need of extra support.“Having access to this real-world data would help us understand how cancer treatments and consultations should be tailored for these individuals, to ensure they feel safe and confident within our healthcare system.“We want everyone in Australia to feel assured that they will always get the best healthcare locally available, irrespective of cultural background. This project is a huge step forward in bolstering that trust within multicultural communities.”Researchers say PROCAP may also be used as a framework in other cancer types, to track the healthcare experiences of CALD women and their treatment experiences in the future.Study participants will be selected through ePAD – a multinational registry that collates demographic, treatment and outcome data of patients with advanced prostate cancer.The project, “PROCAP: Using Patient-Reported Outcome and Experience Measures to Identify and Overcome Disparities in CALD Patients with Advanced Prostate Cancer,” is supported with over $398,000 in funding from Movember’s Personalised Prostate Cancer Care Initiative.Sarah Weller, Global Director of Prostate Cancer at Movember, said: “Movember’s committed to ensuring that every man has access to the best possible prostate cancer care.“The PROCAP study is a critical step toward addressing the healthcare inequities faced by multicultural communities, ensuring that cultural and language barriers don’t stand in the way of better health outcomes.“Through our Personalised Prostate Cancer Care Initiative, we are proud to be funding this groundbreaking research alongside five other global projects, bringing our total investment to $2.1 million.“By supporting studies like PROCAP, we can drive real change in healthcare systems worldwide, ensuring that men receive care tailored to their unique needs and experiences.”

STEM (Science, Tech, Engineering, Math)

Landmark research aims to close cultural gaps in cancer care

WEHI researchers have visualised a key protein complex in malaria parasites for the first time, uncovering a new target for next-generation vaccines that could help stop the disease from spreading.&nbsp;

Using&nbsp;cutting-edge&nbsp;cryo-electron microscopy, the team captured the first detailed structure of a protein complex essential for malaria parasite fertilisation.&nbsp;&nbsp;

The discovery published in&nbsp;Science&nbsp;has led to the development of a promising new mRNA vaccine candidate that stops the malaria parasite from reproducing inside mosquitoes, breaking the cycle of transmission before it can reach humans.&nbsp;

Malaria&nbsp;remains&nbsp;one of the world’s deadliest infectious diseases, responsible for more than 600,000 deaths each year.&nbsp;&nbsp;

WEHI scientists captured the first high-resolution structure of a key protein complex&nbsp;that’s&nbsp;essential for the malaria parasite to reproduce inside mosquitoes.&nbsp;

They discovered two small domains of the Pfs230-Pfs48/45 fertilisation complex that are crucial for the parasite’s ability to fertilise and spread.&nbsp;

A new mRNA vaccine induced antibodies targeting these domains which stopped the parasite from reproducing in mosquitoes, cutting transmission by up to 99.7%.&nbsp;

Visualising malaria’s reproductive machinery&nbsp;

For many years scientists have known that two key proteins that appear on the surface of the malaria parasite, Pfs230 and Pfs48/45, are important for transmission of the disease.&nbsp;

Lead researcher Dr Melanie Dietrich said the new study revealed for the first time how these proteins interact – revealing a new vaccine target.&nbsp;

“Our structural biology approach was the key. Using cryo-electron microscopy, we were able to visualise the full fertilisation complex directly from the parasite – not a lab-made version,” Dr Dietrich, a WEHI postdoctoral fellow said.&nbsp;

"This gave us a clear picture of how this fertilisation complex really looks in&nbsp;nature, and&nbsp;revealed a previously unknown region that’s crucial to the process, unlocking a powerful new vaccine target.”&nbsp;

Lead researcher Professor Wai-Hong Tham said that by capturing the fertilisation complex directly from the parasite, the team revealed the precise contact points that make transmission possible.&nbsp;

"We used these findings to develop a vaccine that showed great promise in targeting these contact points,” Prof Tham, a WEHI laboratory head,&nbsp;said.&nbsp;

“To&nbsp;eliminate&nbsp;malaria, we need to stop transmission. This vaccine candidate could be one piece of that puzzle.”&nbsp;

From structural insight to vaccine innovation&nbsp;

&nbsp;Unlike many structural biology studies that rely on proteins made in the lab from bacterial, insect or mammalian cells, the new research successfully purified the fertilisation complex directly from malaria parasites – a technically challenging approach that ensures the structure reflects its true biological form.&nbsp;

The research revealed the critical contact points for binding the Pfs230 and Pfs48/45 proteins. When these were removed in genetically modified parasites, fertilisation failed and transmission was blocked, illuminating a new vaccine target.&nbsp;

Building on the structural discovery, the team designed a next generation mRNA vaccine which was formulated in collaboration with the mRNA Core facility at the Monash Institute of Pharmaceutical Sciences (MIPS).&nbsp;

In preclinical studies, the vaccine triggered&nbsp;high levels&nbsp;of antibodies that recognised the parasite and blocked transmission in mosquitoes by up to 99.7%.&nbsp;

Professor Colin&nbsp;Pouton&nbsp;from MIPS said it was an exciting opportunity for his team to&nbsp;leverage&nbsp;their&nbsp;expertise&nbsp;in mRNA vaccine development to address&nbsp;an important new target for malaria vaccination.&nbsp;

“Drawing on experience through mRNA Core, the MIPS team shifted focus to tackle a new challenge in malaria vaccination,” Prof&nbsp;Pouton&nbsp;said.&nbsp;&nbsp;

“The success of the malaria vaccine program illustrates the versatility of mRNA technology, which has many applications beyond the COVID vaccines. It was particularly rewarding to work on this project with the WEHI team, co-located in the Parkville precinct,&nbsp;where shared expertise has helped drive a new approach to malaria prevention."&nbsp;

A vulnerable stage in the parasite’s life cycle&nbsp;

Targeting the parasite inside the mosquito offers a strategic advantage due to what researchers call a population bottleneck.&nbsp;&nbsp;

While malaria parasites are abundant in the human host, only a small fraction develop into sexual forms and are successfully fertilised inside the mosquito. This bottleneck means that even modest reductions in parasite numbers at this stage can have a significant impact on transmission.&nbsp;

Transmission-blocking vaccines – like the one designed through this research, targeting the malaria parasite inside the mosquito – offer a strategic way to halt the spread of malaria, where its numbers are lowest and its life cycle most vulnerable.&nbsp;

Multi-stage strategy towards elimination&nbsp;

The team envisions the mRNA vaccine as part of a multi-stage strategy, targeting the parasite in both the mosquito and human host.&nbsp;&nbsp;

By combining transmission-blocking vaccines with those that act on blood or liver stages in people, researchers hope to build a comprehensive defence that could dramatically reduce malaria burden and move closer to elimination.&nbsp;

Prof Tham said the collaboration between WEHI and MIPS highlighted the strength of the Melbourne Biomedical Precinct and the potential of mRNA technology to rapidly translate basic science into vaccine innovation.&nbsp;&nbsp;

“The ability to design, formulate and test vaccine candidates within a single research ecosystem has accelerated the path from discovery to preclinical validation,” she said.&nbsp;

WEHI researchers have visualised a key protein complex in malaria parasites for the first time, uncovering a new target for next-generation vaccines that could help stop the disease from spreading.&nbsp;Using&nbsp;cutting-edge&nbsp;cryo-electron microscopy, the team captured the first detailed structure of a protein complex essential for malaria parasite fertilisation.&nbsp;&nbsp;The discovery published in&nbsp;Science&nbsp;has led to the development of a promising new mRNA vaccine candidate that stops the malaria parasite from reproducing inside mosquitoes, breaking the cycle of transmission before it can reach humans.&nbsp;Malaria&nbsp;remains&nbsp;one of the world’s deadliest infectious diseases, responsible for more than 600,000 deaths each year.&nbsp;&nbsp;At a glance&nbsp;WEHI scientists captured the first high-resolution structure of a key protein complex&nbsp;that’s&nbsp;essential for the malaria parasite to reproduce inside mosquitoes.&nbsp;They discovered two small domains of the Pfs230-Pfs48/45 fertilisation complex that are crucial for the parasite’s ability to fertilise and spread.&nbsp;A new mRNA vaccine induced antibodies targeting these domains which stopped the parasite from reproducing in mosquitoes, cutting transmission by up to 99.7%.&nbsp;Visualising malaria’s reproductive machinery&nbsp;For many years scientists have known that two key proteins that appear on the surface of the malaria parasite, Pfs230 and Pfs48/45, are important for transmission of the disease.&nbsp;Lead researcher Dr Melanie Dietrich said the new study revealed for the first time how these proteins interact – revealing a new vaccine target.&nbsp;“Our structural biology approach was the key. Using cryo-electron microscopy, we were able to visualise the full fertilisation complex directly from the parasite – not a lab-made version,” Dr Dietrich, a WEHI postdoctoral fellow said.&nbsp;"This gave us a clear picture of how this fertilisation complex really looks in&nbsp;nature, and&nbsp;revealed a previously unknown region that’s crucial to the process, unlocking a powerful new vaccine target.”&nbsp;Lead researcher Professor Wai-Hong Tham said that by capturing the fertilisation complex directly from the parasite, the team revealed the precise contact points that make transmission possible.&nbsp;"We used these findings to develop a vaccine that showed great promise in targeting these contact points,” Prof Tham, a WEHI laboratory head,&nbsp;said.&nbsp;“To&nbsp;eliminate&nbsp;malaria, we need to stop transmission. This vaccine candidate could be one piece of that puzzle.”&nbsp;From structural insight to vaccine innovation&nbsp;&nbsp;Unlike many structural biology studies that rely on proteins made in the lab from bacterial, insect or mammalian cells, the new research successfully purified the fertilisation complex directly from malaria parasites – a technically challenging approach that ensures the structure reflects its true biological form.&nbsp;The research revealed the critical contact points for binding the Pfs230 and Pfs48/45 proteins. When these were removed in genetically modified parasites, fertilisation failed and transmission was blocked, illuminating a new vaccine target.&nbsp;Building on the structural discovery, the team designed a next generation mRNA vaccine which was formulated in collaboration with the mRNA Core facility at the Monash Institute of Pharmaceutical Sciences (MIPS).&nbsp;In preclinical studies, the vaccine triggered&nbsp;high levels&nbsp;of antibodies that recognised the parasite and blocked transmission in mosquitoes by up to 99.7%.&nbsp;Professor Colin&nbsp;Pouton&nbsp;from MIPS said it was an exciting opportunity for his team to&nbsp;leverage&nbsp;their&nbsp;expertise&nbsp;in mRNA vaccine development to address&nbsp;an important new target for malaria vaccination.&nbsp;“Drawing on experience through mRNA Core, the MIPS team shifted focus to tackle a new challenge in malaria vaccination,” Prof&nbsp;Pouton&nbsp;said.&nbsp;&nbsp;“The success of the malaria vaccine program illustrates the versatility of mRNA technology, which has many applications beyond the COVID vaccines. It was particularly rewarding to work on this project with the WEHI team, co-located in the Parkville precinct,&nbsp;where shared expertise has helped drive a new approach to malaria prevention."&nbsp;A vulnerable stage in the parasite’s life cycle&nbsp;Targeting the parasite inside the mosquito offers a strategic advantage due to what researchers call a population bottleneck.&nbsp;&nbsp;While malaria parasites are abundant in the human host, only a small fraction develop into sexual forms and are successfully fertilised inside the mosquito. This bottleneck means that even modest reductions in parasite numbers at this stage can have a significant impact on transmission.&nbsp;Transmission-blocking vaccines – like the one designed through this research, targeting the malaria parasite inside the mosquito – offer a strategic way to halt the spread of malaria, where its numbers are lowest and its life cycle most vulnerable.&nbsp;Multi-stage strategy towards elimination&nbsp;The team envisions the mRNA vaccine as part of a multi-stage strategy, targeting the parasite in both the mosquito and human host.&nbsp;&nbsp;By combining transmission-blocking vaccines with those that act on blood or liver stages in people, researchers hope to build a comprehensive defence that could dramatically reduce malaria burden and move closer to elimination.&nbsp;Prof Tham said the collaboration between WEHI and MIPS highlighted the strength of the Melbourne Biomedical Precinct and the potential of mRNA technology to rapidly translate basic science into vaccine innovation.&nbsp;&nbsp;“The ability to design, formulate and test vaccine candidates within a single research ecosystem has accelerated the path from discovery to preclinical validation,” she said.&nbsp;

Medical / Hospital

Revealed: new vaccine target to block malaria transmission

WEHI researchers have made a huge leap forward in the fight against Parkinson’s disease, solving a decades-long mystery that paves the way for development of new drugs to treat the condition.

First discovered over 20 years ago, PINK1 is a&nbsp;protein&nbsp;directly&nbsp;linked to&nbsp;Parkinson’s disease – the fastest growing neurodegenerative condition in the world. Until now, no one had seen what human PINK1 looks like, how PINK1 attaches to the surface of damaged mitochondria, or how it is switched on.&nbsp;

In&nbsp;a major breakthrough, researchers at the WEHI Parkinson’s Disease Research Centre have determined the first ever structure of human PINK1 bound to mitochondria, in findings published in&nbsp;Science. The work could help find new treatments for the condition that currently has no cure or drug to stop its progression.

In a world-first, WEHI researchers have discovered what human PINK1 looks like and how it is activated.PINK1 is a protein linked to Parkinson’s disease, the second most common neurodegenerative disease after Alzheimer’s.There is no cure for Parkinson’s.This discovery, published inScience, is a huge leap forward in the fight against Parkinson’s with the hope that it will accelerate the search for a drug to stop the condition.

Parkinson’s disease is insidious, often taking years, sometimes decades to diagnose. Often associated with tremors, there are close to 40 symptoms including cognitive impairment, speech issues, body temperature regulation and vision problems.

In Australia, over 200,000 people live with Parkinson’s and between 10% and 20% have Young Onset Parkinson’s Disease – meaning they are diagnosed under the age of fifty. The impact of Parkinson’s on the Australian economy and healthcare systems is estimated to be over $10 billion each year.

Mitochondria produce energy at a cellular level in all living things, and cells that require a lot of energy can contain hundreds or thousands of mitochondria. The PARK6 gene encodes the PINK1 protein, which supports cell survival by detecting damaged mitochondria and tagging them for removal.

In a healthy person, when mitochondria are damaged, PINK1 gathers on mitochondrial membranes and signals through a small protein called ubiquitin, that the broken mitochondria need to be removed. The PINK1 ubiquitin signal is unique to damaged mitochondria, and when PINK1 is mutated in patients, broken mitochondria accumulate in cells.

Although PINK1 has been linked to Parkinson’s, and in particular Young Onset Parkinson’s Disease, researchers had been unable to visualise it and did not understand how it attaches to mitochondria and is switched on.

Corresponding author on the study and head of WEHI’s Ubiquitin Signalling Division, Professor David Komander, said years of work by his team have unlocked the mystery of what human PINK1 looks like, and how it assembles on mitochondria to be switched on.

“This is a significant milestone for research into Parkinson's. It is incredible to finally see PINK1 and understand how it binds to mitochondria,”&nbsp;said Prof Komander, who is a laboratory head in the WEHI Parkinson’s Disease Research Centre.

“Our structure reveals many new ways to change PINK1, essentially switching it on, which will be life-changing for people with Parkinson’s.”

Lead author on the study, WEHI senior researcher Dr Sylvie Callegari, said PINK1 works in four distinct steps, with the first two steps not been seen before.

First, PINK1 senses mitochondrial damage. Then it attaches to damaged mitochondria. Once attached it tags ubiquitin, which then links to a protein called Parkin so that the damaged mitochondria can be recycled.

“This is the first time we’ve seen human PINK1 docked to the surface of damaged&nbsp;<a target="_blank">mitochondria</a>&nbsp;and it has uncovered a remarkable array of proteins that act as the docking site. We also saw, for the first time, how mutations present in people with Parkinson’s disease affect human PINK1,” said Dr Callegari.

The idea of using PINK1 as a target for potential drug therapies has long been touted but not yet achieved because the structure of PINK1 and how it attaches to damaged mitochondria were unknown.

The research team hope to use the knowledge to find a drug to slow or stop Parkinson’s in people with a PINK1 mutation.

One of the hallmarks of Parkinson’s is the death of brain cells. Around 50 million cells die and are replaced in the human body every minute. But unlike other cells in the body, when brain cells die, the rate at which they are replaced is extremely low.

When mitochondria are damaged, they stop making energy and release toxins into the cell. In a healthy person, the damaged cells are disposed of in a process called mitophagy.

In a person with Parkinson’s and a PINK1 mutation the mitophagy process no longer functions correctly and toxins accumulate in the cell, eventually killing it. Brain cells need a lot of energy and are especially sensitive to this damage.

The study, “Structure of human PINK1 at a mitochondrial TOM-VDAC array”, is published in&nbsp;Science&nbsp;(DOI:&nbsp;<a href="https://doi.org/10.1126/science.adu6445" target="_blank">10.1126/science.adu6445</a>).

WEHI researchers have made a huge leap forward in the fight against Parkinson’s disease, solving a decades-long mystery that paves the way for development of new drugs to treat the condition.First discovered over 20 years ago, PINK1 is a&nbsp;protein&nbsp;directly&nbsp;linked to&nbsp;Parkinson’s disease – the fastest growing neurodegenerative condition in the world. Until now, no one had seen what human PINK1 looks like, how PINK1 attaches to the surface of damaged mitochondria, or how it is switched on.&nbsp;In&nbsp;a major breakthrough, researchers at the WEHI Parkinson’s Disease Research Centre have determined the first ever structure of human PINK1 bound to mitochondria, in findings published in&nbsp;Science. The work could help find new treatments for the condition that currently has no cure or drug to stop its progression.<h2>At a glance</h2>In a world-first, WEHI researchers have discovered what human PINK1 looks like and how it is activated.PINK1 is a protein linked to Parkinson’s disease, the second most common neurodegenerative disease after Alzheimer’s.There is no cure for Parkinson’s.This discovery, published inScience, is a huge leap forward in the fight against Parkinson’s with the hope that it will accelerate the search for a drug to stop the condition.Parkinson’s disease is insidious, often taking years, sometimes decades to diagnose. Often associated with tremors, there are close to 40 symptoms including cognitive impairment, speech issues, body temperature regulation and vision problems.In Australia, over 200,000 people live with Parkinson’s and between 10% and 20% have Young Onset Parkinson’s Disease – meaning they are diagnosed under the age of fifty. The impact of Parkinson’s on the Australian economy and healthcare systems is estimated to be over $10 billion each year.Breakthrough after decades of researchMitochondria produce energy at a cellular level in all living things, and cells that require a lot of energy can contain hundreds or thousands of mitochondria. The PARK6 gene encodes the PINK1 protein, which supports cell survival by detecting damaged mitochondria and tagging them for removal.In a healthy person, when mitochondria are damaged, PINK1 gathers on mitochondrial membranes and signals through a small protein called ubiquitin, that the broken mitochondria need to be removed. The PINK1 ubiquitin signal is unique to damaged mitochondria, and when PINK1 is mutated in patients, broken mitochondria accumulate in cells.Although PINK1 has been linked to Parkinson’s, and in particular Young Onset Parkinson’s Disease, researchers had been unable to visualise it and did not understand how it attaches to mitochondria and is switched on.Corresponding author on the study and head of WEHI’s Ubiquitin Signalling Division, Professor David Komander, said years of work by his team have unlocked the mystery of what human PINK1 looks like, and how it assembles on mitochondria to be switched on.“This is a significant milestone for research into Parkinson's. It is incredible to finally see PINK1 and understand how it binds to mitochondria,”&nbsp;said Prof Komander, who is a laboratory head in the WEHI Parkinson’s Disease Research Centre.“Our structure reveals many new ways to change PINK1, essentially switching it on, which will be life-changing for people with Parkinson’s.”Hope for future treatmentsLead author on the study, WEHI senior researcher Dr Sylvie Callegari, said PINK1 works in four distinct steps, with the first two steps not been seen before.First, PINK1 senses mitochondrial damage. Then it attaches to damaged mitochondria. Once attached it tags ubiquitin, which then links to a protein called Parkin so that the damaged mitochondria can be recycled.“This is the first time we’ve seen human PINK1 docked to the surface of damaged&nbsp;<a target="_blank">mitochondria</a>&nbsp;and it has uncovered a remarkable array of proteins that act as the docking site. We also saw, for the first time, how mutations present in people with Parkinson’s disease affect human PINK1,” said Dr Callegari.The idea of using PINK1 as a target for potential drug therapies has long been touted but not yet achieved because the structure of PINK1 and how it attaches to damaged mitochondria were unknown.The research team hope to use the knowledge to find a drug to slow or stop Parkinson’s in people with a PINK1 mutation.The link between PINK1 and Parkinson’sOne of the hallmarks of Parkinson’s is the death of brain cells. Around 50 million cells die and are replaced in the human body every minute. But unlike other cells in the body, when brain cells die, the rate at which they are replaced is extremely low.When mitochondria are damaged, they stop making energy and release toxins into the cell. In a healthy person, the damaged cells are disposed of in a process called mitophagy.In a person with Parkinson’s and a PINK1 mutation the mitophagy process no longer functions correctly and toxins accumulate in the cell, eventually killing it. Brain cells need a lot of energy and are especially sensitive to this damage.The study, “Structure of human PINK1 at a mitochondrial TOM-VDAC array”, is published in&nbsp;Science&nbsp;(DOI:&nbsp;<a href="https://doi.org/10.1126/science.adu6445" target="_blank">10.1126/science.adu6445</a>).