Open PhD position 2026/2027

Spinal cord injury treatment with immunomodulatory exosomes and second generation PI3Kdelta gene therapy

A complex pathology such as spinal cord injury (SCI) requires a complex therapeutic approach. In this project, we will work to isolate exosomes from neural precursor cells (SPC-NPs) which contain neuroprotective factors, and we will enhance their therapeutic capability to treat SCI by loading them with small interfering RNA against inflammasome NLRP3. The NLRP3 inflammasome is activated in both neurons and glial cells after SCI and causes their death and the production of pro-inflammatory cytokines which perpetuates the secondary pathologies. In addition, we will modify the surface of exosomes so that they bind to the injury associated molecule chondroitin sulphate proteoglycans at the lesion site. This modification will ensure the accumulation of modified exosomes to deliver anti-inflammatory and neuroprotective intervention in the acute phase of SCI, in the first week after injury. Subsequently, we will combine this first tier treatment with second-tier gene therapy in which we will use an AAV1-SYN-PIK3CDE1021K delivered to the cortical motor neurons. This will result in the production of second generation PI3Kdelta gene therapy using a modified PI3Kdelta, which spontaneously relocates to the cell membrane and triggers PI3K/mTOR signaling more robustly than PI3Kdelta without the modification, and which stimulates axon regeneration and functional improvement, but with delayed onset. In this project, we hope to use exosomes to protect the spinal tissue and prepare it for a more robust and rapid axon regeneration following PI3Kd E1021K gene therapy. The PhD student will learn cell culture techniques to produce and isolate SPC-NP exosomes. They will learn to modify their surface and load them and will work to optimize protocols for long term storage. They will then test the effects of exosomes in the culture of spinal interneurons. The PhD student will learn animal handling and relevant surgical techniques (SCI, intrathecal application of exosomes, AAV cortical injections) which they will use in the project, including behavioral testing. They will evaluate spinal and brain tissue with immunohistochemistry and microscopy.

We are looking for an eager MSc graduate in biology, biochemistry or biotechnology to join our team. The ideal candidate is driven to learn about spinal cord injury and the methods needed in SCI therapy development. They will have the ability and confidence to self-manage, plan and execute scientific tasks involving cell culture, animal handling, protein analysis techniques and microscopy.

• MSc degree in biological sciences
• English speaker, able to communicate effectively with supervisor and team members
• Motivated, curious, responsible, committed to professional development

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