Morse projects

Focused ultrasound and microbubbles is a technique that can non-invasively, locally and temporarily open the blood-brain barrier to allow drugs into the brain. The way this technology works is by injecting clinically-approved microbubbles and drugs into the bloodstream. When the microbubbles reach the area where the ultrasound is targeted in the brain, these bubbles oscillate, mechanically stimulating the blood vessels, allowing the barrier to open so that drugs can enter the brain.

But what happens to the microglia when the blood-brain barrier is open? Microglia are the innate immune cells of our brain. They actively survey the brain and clear away toxins and pathogens. In this project, you will explore the effect that opening the blood-brain barrier has on microglia: phagocytosis, antigen-presentation, activation level. Immunohistochemical staining for various markers of microglial activity will be used to visualise changes in their morphology and activity. Microscopy images will be assessed to explore how microglia are affected by this non-invasive drug delivery technique.

Sophie Morse

Microglia are the innate immune cells of our brain. They actively survey the brain and clear away toxins and pathogens. The ability to temporarily stimulate microglia has the potential to help treat brain diseases, such as brain tumours, Alzheimer’s disease and Parkinson’s disease. For example, stimulating microglia can help clear away amyloid-beta plaques that accumulate in Alzheimer’s disease brains.

Focused ultrasound is a non-invasive technique that has been used to stimulate neurons. However, we have discovered that microglia can also be affected depending on the way ultrasound is emitted. In this project, the level of microglia activation will be assessed for a variety of different ultrasound exposure parameters. Staining for various markers of microglia and their activation will be used to visualise changes in their morphology and activation level. Microscopy images will be assessed to explore what ultrasound can achieve in terms of microglial modulation with this non-invasive ultrasound technology.

Sophie Morse

Astrocytes, together with endothelial cells, are the gatekeepers of the brain’s main security system – the blood-brain barrier. They control which substances enter and exit the brain, and keep harmful substances out. Astrocytes also regulate blood flow to transport nutrients to neurons depending on their energy needs. These cells are at the forefront of our thought processes: they regulate our synapses, and recycle and secrete neurotransmitters.

The ability to temporarily stimulate astrocytes has the potential to help treat brain diseases, such as Alzheimer’s disease and Parkinson’s disease. Focused ultrasound is a non-invasive and targeted technique that has been used to stimulate neurons. However, we have discovered that the activity of astrocytes can also be modulated depending on the way ultrasound is emitted.

In this project, the level of astrocyte activation will be assessed for a variety of different ultrasound exposure parameters. Staining for various markers of astrocytes and their activation will be used to visualise (with microscopy) changes in their morphology and activation level. This project will lead to key advances in the unexplored territory of how the activity of the brain’s gatekeepers can be non-invasively modulated with ultrasound to treat brain diseases.

Sophie Morse

Focused ultrasound and microbubbles is a technique that can non-invasively, locally and temporarily open the blood-brain barrier to allow drugs into the brain. The way this technology works is by injecting clinically-approved microbubbles and drugs into the bloodstream. When the microbubbles reach the area where the ultrasound is targeted in the brain, these bubbles oscillate, mechanically stimulating the blood vessels, allowing the barrier to open so that drugs can enter the brain.
But how do astrocytes respond to this blood-brain barrier opening? In this project, you will explore whether astrocytes are activated during this opening procedure. Immunohistochemical staining for various markers of astrocyte activation will be used to visualise changes in their morphology and activation level. Microscopy images will be assessed to explore how ultrasound is affecting astrocyte behaviour during this non-invasive therapeutic procedure.

Sophie Morse

Our brain has a security system, called the blood-brain barrier, which protects our neurons from harmful substances, but also prevents over 98% of drugs from entering. Focused ultrasound is an exciting technology that has been shown to allow drugs to be delivered to the brain non-invasively and in a targeted manner. It works in combination with clinically approved microbubbles that circulate through the bloodstream and only when they reach the area where the ultrasound has been focused, they oscillate, generating mechanical forces on the vessel walls, opening the barrier and allowing drugs to be delivered to that region. Currently, there are multiple clinical trials ongoing around the world that are showing really promising efficacy and safety results, giving hope to many people with brain diseases.

When emitting different types of ultrasound sequences to deliver different drugs, we are unaware of the effect that these treatments could have on neuronal activity. In particular, we have developed a sequence that involves the emission of very short pulses of ultrasound, which has shown to deliver drugs more efficiently and with a higher safety profile. We are particularly interested in knowing how this short pulse sequence affects neuronal signalling.

This lab-based project will involve sectioning brains and imaging these sections with confocal microscopy to visualise any changes in the number of dendritic spines, which are the small protrusions from neuron’s dendrites that receive inputs from axons at the synapse. The mice that we are using have been genetically engineered to express GFP+ve fluorescent neurons, which allows the visualisation of the dendrites. Experience with immunohistochemical staining as well as confocal microscopy will be gained. This project will unravel the effect that these ultrasound treatments may have on neurons, which will bring insight into the unknown biological effects that ultrasound treatments have on the brain.