Seeds for Seed Award

Principal Investigator: Dr Matthias Gruber
School of Psychology

In everyday life, learning is often self-motivated and we actively seek information that is of interest to us. For example, we spend hours online searching for information that sparks our curiosity. Despite the importance of curiosity in every-day life, we know very little about how curiosity changes the brain and why it actually is that curiosity improves learning. Instead, research has mostly studied learning and memory when participants passively encode information with little control about what and when to encode information. Therefore, the current project aims to develop an experimental approach to study curiosity-guided learning in the laboratory using virtual reality (VR).

In the experiment, participants will navigate a virtual environment in which they virtually explore familiar and novel rooms. The experiment will allow investigating how exploration and curiosity affects how we learn and remember information. In future studies, the developed experiment will allow addressing key questions about the neural mechanisms of curiosity-based learning. The developed VR experiment has promise to be further developed into a mobile app that could be widely used to measure biomarkers in children and patients who might benefit from curiosity-guided learning.

Principal Investigator: Dr Danijela Tatovic
School of Medicine

Type 1 diabetes (T1D) is caused when cells of the immune system called T-cells attack and destroy insulin-producing cells in the pancreas. Monitoring of these pivotal immune cells is currently highly challenging, as we cannot see what is happening in the pancreas. We have developed ways to monitor T-cell activity by studying organs called lymph nodes that act as ‘stations’ on the transport network that T-cells use to travel around the body. These lymph nodes provide a window into what is happening in the pancreas during disease and allow monitoring of events during clinical trials. The technique we developed involves the use of a very fine needle that is guided using ultrasound.

We now wish to use it to monitor the Tcells responsible for killing to insulin-producing cells using state-of-the-art technologies developed by my collaborators who are world-leading experts in Tcells during T1D. This funding will allow us to obtain important preliminary data and develop new collaborations that will represent a solid base for larger project aimed at establishing new methods for monitoring T-cells during immunotherapy trials.

Principle Investigator: Dr Emre Kopanoglu
School of Psychology

Magnetic Resonance Imaging (MRI) provides valuable diagnostic information. MRI scans may last several minutes, and patient motion makes data inconsistent, leading to scan repetitions. Motion may be especially unavoidable with children and patients with Parkinson’s, Huntington’s or dementia. Using sedatives carries risk and mid-acquisition motion correction techniques have so far only been developed for conventional MRI scanners.

Recently developed ultra-high field (UHF)-MRI scanners offer significantly higher quality images but suffer from artificial contrast variations across the image. Motion also makes these contrast variations inconsistent throughout the scan, reducing the effectiveness of current motion correction methods.

The extent of these UHF-MRI specific effects of motion is currently unknown. Our initial simulations show that even a 5mm head-motion can locally change acquired signal by more than 50%. This poses severe data-inconsistency problems for structural and functional MRI. We will investigate the severity and characteristics of effects of motion on UHF-MRI via participant scans. The results of this study will support development of a research programme on correcting these effects. A key area to benefit would be functional MRI of movement-prone patients, since head motion is commonly problematic, and sedatives cannot be used as they themselves affect brain function.

Principal Investigator: Dr Cedric Berger
School of Biosciences

Diarrheal disease is the second leading cause of death in children under five years of age. Multiple microbes may be responsible for these infections but the majority of diarrheal cases are associated with bacteria called Escherichia coli. These bacteria can be found in contaminated water and food. After they have been eaten, they colonise the gut, cause inflammation and stop food absorption leading to malnutrition, which can be fatal, especially in children in the poorest countries.

Certain Escherichia coli strains inject their own proteins, named effectors, into the human cells to promote disease. These effectors hijack the different cell functions (e.g. promote inflammation) for the benefit of the bacteria.  We have recently identified potential new cell functions that could be altered by the bacteria.

This project will use a model system to understand how effector proteins work and develop a test to understand how these harmful bacteria affect bowel cells, ultimately aiming to develop strategies to prevent enteric infection.

Principal Investigator: Dr Ben Newland
School of Pharmacy and Pharmaceutical Sciences

Stem cell therapies hold the potential to halt, or reverse, the progression of diseases such as Parkinson’s or Huntington’s disease. However, when cells are injected into the brain, the majority of them die very quickly, a problem that needs to be addressed for successful widespread use in the clinic.

There are several plausible reasons why the cells die after transplantation, however, we have recently shown that a lack of glucose could be the biggest problem facing freshly transplanted cells. This lack of glucose occurs in the early stages post transplantation before blood vessels grow into the graft, and it is specifically glucose that plays the vital role.

We would use this grant money to collect two sets of pilot data. Firstly to prove that glucose is the vital component for the stem cells used in Parkinson’s and Huntington’s disease research. Secondly, to prove that glucose can be released from hydrogels in a controlled manner. No one has yet developed glucose releasing materials, but we have an idea how to do this. The data generated in this project will be used as evidence in future grant applications, where we will ask for substantial funding to create the world’s first injectable glucose supply.

Principal Investigator: Dr Meike Heurich
School of Pharmacy and Pharmaceutical Sciences

We aim to generate a new treatment strategy for inflammatory and thrombotic diseases to simultaneously dampen an excessive response of the immune and clotting system. Both complement (immunity) and coagulation (clotting) work together, to keep blood vessels healthy. However, in disease, this protection is dysfunctional. Uncontrolled, excessive activation in blood vessels leads to tissue destruction and clot formation, causing, for example, a heart attack or stroke. Complement and coagulation blood protein cascades need to be appropriately regulated. One of our body’s control proteins on the surface of blood vessels, thrombomodulin, protects them from damage through uncontrolled blood clotting.

Our research has shown that thrombomodulin also controls complement immunity. We have characterised the interaction sites between thrombomodulin and complement protein factor H. We utilize computational methods to model this interaction and pre-screen and select suitable thrombomodulin mutants with enhanced complement factor H regulating activity - while maintaining its coagulation regulatory function.

Cell culture for recombinant protein expression is established for wildtype protein and lead candidate(s) will be generated, purified and tested in standard complement and clotting activation assays using specialist equipment. In the future, this dual-target therapeutic will be assessed in vivo with the aim to become integrated into a clinical trial.