The role of Blastocystis in inflammatory bowel disease (324516).

When people suffer from severe intestinal problems, the hospital often examines the patient's stool to look for clues. If the hospital lab finds small organisms called microbial eukaryotes, they are often thought to be the cause of the disease and the patient is given medication to eliminate these parasites. This proposal focuses on one such parasite called Blastocystis because we have doubts about whether it is actually a parasite. Previous studies using small groups of people have found this ‘parasite’ in a large proportion of people without intestinal problems. Also, when we give this parasite to rats that have severe intestinal disease, symptoms are less severe compared to rats that have not been given Blastocystis.

To prevent people being treated for something that did not make them sick, we want to investigate this matter thoroughly. We will be looking for the distribution of Blastocystis in a large Danish study group that includes over 7,000 people. This background population will be the largest study of the distribution of Blastocystis ever. We will also be looking for Blastocystis in a large 700 patient Norwegian clinical trial of inflammatory bowel disease. We will also try to find out whether cancer patients receiving immunotherapy are more or less likely to develop severe bowel disease (as an adverse side effect) if they have Blastocystis or not. Finally, we will conduct comparative studies in a rat model that we can infect with Blastocystis and then induce bowel disease, as this will allow us to study in a controlled manner whether Blastocystis makes symptoms better or worse.

We hope that our thorough investigations with a large interdisciplinary team of clinicians, molecular biologists, epidemiologists, and animal scientists will eventually allow us to inform hospitals whether they should treat patients when they find Blastocystis or whether they need to look further for the real cause of the patients' symptoms.

Mitochondrial glycolysis as a target for disease control of pathogenic stramenopiles (301170).

Disease seriously affects humans, animals and plants. In the case of livestock and crops, such diseases impact on the provision of food. The world population is expected to reach 9 to 10 billion within the next 30 years, so we need to produce more food than we currently do. Diseases therefore limit our ability to produce the food we need.

We recently discovered a peculiar feature in a large group of organisms, which include several pathogens of humans, animals and crops. Normally, the food we consume is broken down in simple compounds such as the sugar glucose. This glucose is metabolised into smaller molecules leading to the production of the energy molecule ATP. This breakdown of glucose happens in the main compartment of the cell called the cytoplasm, while the bulk of the ATP production takes place in a special compartment called the mitochondrion.

We discovered that in some organisms the breakdown of glucose takes place in the ATP-producing mitochondria. This is quite unexpected and raises the question what the reason is for this peculiarity. In addition, this also means that a different molecule needs to be transported into the mitochondrion to make this possible. As this transport is normally tightly controlled by very special transporters, this means that a special transporter will be required to make sure the energy provision of these organisms can take place.

We aim to identify and characterise this special transporter with the aim to use it as a new drug target. This drug target is present in a human intestinal parasite and also in important animal and plant pathogens, and would allow for the specific targeting of these pathogens while not affecting their hosts.

Our project will elucidate the nature of this unusual metabolic phenomenon and provide insight in the evolution and biochemistry of this transporter with the aim to produce novel therapeutics to combat important pathogens.

PREDICTOM - Prediction of Alzheimer’s disease using an AI driven screening platform (101132356).

Dementia affects growing numbers of people worldwide. There are now treatments designed to slow the progress of the disease, however these are likely to be most effective when given in the very earliest stages of the disease. The challenge is most people are only diagnosed once their symptoms are quite advanced. Furthermore, diagnosing dementia currently involves invasive and costly tests such as PET (positron emission tomography) scans and analyses of cerebrospinal fluid (CSF).

The goal of the PREDICTOM project is to develop a screening platform capable of identifying people at risk of dementia, before the first symptoms appear. Crucially, patients would be able to start the screening process from the comfort of their own homes. They could collect samples of bodily fluids, and use digital technologies to gather results (e.g. smartphone-based eye tracking and cognitive tests).

Samples will be sent to the PREDICTOM partners’ laboratories, and then to the PREDICTOM platform for processing of the data. Algorithms based on artificial intelligence (AI) would then assess the person’s risk of developing dementia and their prognosis. In this way, the platform will facilitate the early diagnosis of a wider range of people, enabling earlier intervention and hopefully slowing progress of the disease.

Over 4 000 people from across Europe will take part in the PREDICTOM study. The project brings together industry, academia, patient groups and hospitals.