Our funding

Croatian Science Foundation

CANDiD: Characterisation of aggregating proteins in neuropsychiatic diseases, including Drosophila models”
ISkrEN: Istraživanje shizofrenije kroz ekspresiju netopivih proteina
Project leader: Dr. Nicholas Bradshaw, PhD
Project associates: Dr. Rozi Andretić Waldowski, MD PhD, Dr. Aristea Pavešić Radonja, MD, Prof. Gordana Rubeša, MD PhD, Beti Zaharija, MSc, Bobana Samardžija, MSc, Giovanna Dashi, BSc,
Tina Fartek, BSc, Anja Hart, BSc.
Duration: 11/2018-03/2023
Funder: Croatian Science Foundation (Hrvatska zaklada za znanost, HRZZ), project grant IP-2018-01-9424
 
While mental illnesses such as schizophrenia, major depression and bipolar disorder have devastating effects on patients and those around them, we still know relatively little about their biological causes. A major problem has been that the genetic background of these illnesses is extremely complex: with many different genes involved, but few having more than a small individual effect on whether someone develops the illness or not. We, along with our collaboration partners, have therefore been working on an alternative method of studying the biology of these disorders. In many other diseases of the brain, such as Alzheimer’s disease or Parkinson’s disease, specific proteins fold incorrectly in the brain, and instead build up in unfolded clusters in the brain, called aggregates. Some of these aggregates are toxic, and actively kill the cells of the brain, while others instead prevent the cells from functioning normally. We and others have therefore been investigating whether similar protein aggregates appear in the brains of patients with life-long mental illnesses. So far, a total of five proteins have been found to aggregate in schizophrenia and/or other conditions, named CRMP1, DISC1, dysbindin-1, NPAS3 and TRIOBP-1.
 
Our HRZZ project therefore has five main aims:
 
1) We know that in the case of TRIOBP-1 and NPAS3, very specific sections of the protein are required for them to aggregate – with deletion or mutation of these sections affecting whether or not they form aggregates. Using molecular and cellular biology techniques, we are now investigating whether similar “aggregation critical” sites exist on the other three proteins, to better understand how aggregation occurs.
 
2) Each of the proteins that we study has been seen to form aggregates alone in mental illness, but there is also evidence, at least in some cases, that they can also bind to each other to form “co-aggregates” which might jointly affect neurons, and ultimately mental illness. We are therefore systematically investigating the interactions, and co-aggregation, of these proteins.
 
3) One we know that aggregation does occur in mental illness, the next stage is to determine whether aggregation itself can directly affect the way we think and our behaviour. As a first test of this, we are collaborating with the laboratory of Dr. Rozi Andretić Waldowski to test the effect of aggregation of our proteins in a simple organism: the fruit fly Drosophila.
 
4) While it is interesting to know if each of our proteins can affect neurons or fruit flies when they begin to aggregate, our aim is to understand how they co-operate together to have effect on mental illness. We will therefore study the affects of these proteins in combination on cell function and behaviour.
 
5) The study of protein aggregation in mental illness is still very new, and has been reported so far in only a small number of patients. Therefore, through collaborations with the Psychiatry Clinic or our local hospital, along with research institutes abroad, we are continuing to investigate the presence of protein aggregates in samples donated by patients with a variety of mental illnesses.
 
Additionally, Beti Zaharija and Bobana Samardžija are being supported by a PhD student stipends from the HRZZ: DOK-2018-09-5395 (2019-2023) and DOK-2020-01-8580 (2020-2024)
 
Equipment grants

Equipment throughout the Department of Biotechnology, including in our labs was funded by the European Union, through the European Regional Development Fund grant “Razvoj istraživačke infrastrukture na Kampusu Sveučilišta u Rijeci” (Developing research infrastructure at the Campus of the University of Rijeka, RC.2.2.06.0001) 

Additionally, as an alumni of the Alexander von Humboldt Foundation (postdoctoral fellowship 2011-2014), Dr. Bradshaw received an equipment subsidy from the Foundation to help establish the research group, and which was presented by the Political Attaché of the German Embassy in Croatia.
 
ERASMUS exchanges
Students in the Bradshaw group have so far been highly successful in winning ERASMUS+ traineeships. Beti Zaharija performed an 8-month traineeship in 2019 to the University of Edinburgh, to work in the group of Dr. Kirsty Millar, while Bobana Samardžija performed a traineeship in 2020 at the Jülich Research Centre (Froschungszentrum Jülich) under the supervision of Dr. Oliver Weiergräber.
 
Previous funding
Our group has received two grants from the University of Rijeka to support our work (young researcher’s grant 969, stimulation funding 1157). Previous funding to Dr. Bradshaw has come from the Fritz Thyssen Foundation, the Alexander von Humboldt Foundation and the Heinrich Heine University Düsseldorf.