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SIV vingill: Modelling α-synuclein Parkinson’s pathology in CRISPR-engineered human iPSC-derived dopamine neurons

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At the start of the day, Professor Andrew King introduced the first speaker, Dr Siv Vingill, a Postdoctoral Research Scientist from the Wade-Martins Group. Her talk addressed            α-synuclein, a presynaptic neuronal protein that is linked genetically and neuropathologically to Parkinson's. Siv's team is trying to establish a model where they can look at how            α-synuclein is transmitted in human dopamine neurons and with the modifications that are present in human patients. Having created the model, "we've looked at how α-synuclein is transported and we're looking at the difference between different patient mutations and control cells." (Dr Vingill).

Anna hoerder-suabedissen: SNAP25 cKO impacts late steps in circuit formation but not early axon outgrowth and targeting

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Next up was Dr Anna Hoerder-Suabedissen, a Postdoctoral Research Scientist working across the Szele and Molnar labs. Anna's team uses a particular model to observe the effects of knocking out the protein SNAP25 on the developing brain. Her talk delivered the key message that many of the processes understood to require cellular activity in the developing brain do not appear to require it to the extent as initially thought. She demonstrated that "SNAP25 was known to be very important in excitatory neurons for synaptic transmission, but there were lots of complications saying it's not involved at all in interneurons in any way shape or form, and our supplementary material showed that you can very much interfere with synaptic transmission in interneurons by knocking out SNAP25, which is a big conceptual shift in the field." (Dr Hoerder-Suabedissen).

Strikingly, the first two talks of the day were linked by alternative perspectives on the role of α-synuclein. In Parkinson's, α-synuclein aggregates are shown to damage the neurons, whereas Anna mentioned that some of the impairment caused by reduction in or misfolding of SNAP25 protein can be ameliorated by higher levels of α-synuclein (Ref: Sharma et al., 2012).

aaron allen: Inferring cellular identity and physiology by single-cell transcriptomic analysis of Drosophila male and female central nervous system

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The third talk of the day was delivered by Dr Aaron Allen, a Postdoctoral Researcher from the Goodwin Group. His talk described how he is looking at how many different types of cells there are in the nervous system and whether we can see any differences between the male and female nervous system. "Hopefully, based on what that tells us, we can look and see how might that nervous system be differentially set up between males and females to lead to differences in behaviour". (Dr Allen). 

jackson smith: Information limiting correlations in simultaneous V1 and V4 responses in binocular disparity stimuli

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After a short break, the audience reconvened to hear Postdoctoral Research Scientist Dr Jackson Smith from the Parker Group. Jackson explored the basic question of how the brain passes information accurately from one area of the cerebral cortex to another. He studied how neurons in the macaque visual cortex support the perception of stereoscopic depth. He noted that if the brain contains noise it can't get rid of, then a person's ability to see depth may be diminished.  "The results I presented suggest that the brain might have a mechanism for cleaning up noisy, correlated signals. Such a mechanism would mean that we see a much more accurate depiction of depth than might otherwise be the case. It appears that the brain may be able to overcome some of the limits that might be imposed by correlated noise." (Dr Smith).

samuel nayler: Dissecting and directing cerebellar ontogenesis—towards an organoid model for understanding disease of the cerebellum

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The audience next heard from Oxford Nuffield Medical Fellow and Becker Group member, Samuel NaylerSamuel's main goal is to make a cerebellum-like tissue from human induced pluripotent stem cells. His talk demonstrated that growing human stem cells together in the right conditions with the right growth factors allows them to self organise into an organ-like tissue known as an organoid. Having validated that there are human cerebellar neurons present in these organoids, he is using single-cell sequencing of the organoids to see which genes are expressed in each cell, enabling him to trace them back to learn the identity and maturity of each cell. Commenting on the talk, group leader Associate Professor Esther Becker said: "By doing that he has shown that you really get all major cell types of the cerebellum in these organoids that started out as stem cells. This is amazing as that's something that usually happens in utero in the developing foetus. It is a major achievement by Sam that we can start to recreate this process in the lab."

BRADLEY ROBERTS: Striatal GABA transporter activity governs dopamine release: implications for Parkinson’s disease

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Next up was Bradley Roberts, a DPhil student working in the Cragg Group, who discussed his work looking into how dopamine release in the brain region called the striatum is controlled. In Parkinson’s dopamine release is reduced and causes debilitating motor symptoms. "Through my DPhil research we have found that extracellular ‘ambient’ GABA in the striatum can inhibit dopamine release and that the levels of this ambient GABA are controlled by astrocytes. Astrocytes are another cell type in the brain (they are not neurons) and surround themselves within dopamine release sites.  Within this role they work to hoover up this extracellular 'ambient' GABA in striatum through GABA transporters which they express. Strikingly, we have found that in Parkinson’s disease models that these astrocytes are dysfunctional and lose their ability to hoover up this GABA, which results in maladaptive increased inhibition of dopamine release. We are excited by these findings as they could present a novel therapeutic avenue for up-regulating dopamine signalling in Parkinson’s disease." (Bradley Roberts).

francis szele: Adult Neurogenesis and Neuropsychiatric Disorders

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After lunch, the audience heard from Prof Francis Szele, Associate Professor of Developmental Biology, who gave a talk discussing the brain changes involved in Schizophrenia and Autism disorders, and introduced new research from his group identifying the biggest neural change in these two diseases.

ANDREW SHELTON: Exploring the ‘hidden space’: structure and function of the mouse claustrum

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Next, Graduate Student Andrew Shelton from the Butt and Packer groups presented his work looking at the Claustrum, which he explained is one of the most heavily interconnected structures in the brain and yet we still know relatively little about it. "My project overall is to address the connectivity and cell types in the claustrum to gain a better idea of how they might be contributing to cortical processing". (Andrew Shelton).

alex ivanov: Exploring the ‘hidden space’: structure and function of the mouse claustrum

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The next speaker was the Walker and King groups' Alex Ivanov, a Graduate Student who, as part of the auditory neuroscience group, studies how we perceive sounds and how we adapt to sounds in health and disease. Alex's topic focuses on using computational and experimental approaches to try and understand how we adapt to environments which have different amounts of echo (reverberation). "We’ve done that by first building a model of the adaptation process, then testing our model using different experimental approaches in ferrets, and we are hoping to also carry out a human psychophysics task to validate our findings. In terms of the impact, I think it would be quite relevant for helping us to improve hearing aids  and speech recognition algorithms, because they all suffer when the environment becomes more echoic." (Alex Ivanov)

johannes dahmen: Connectivity and function of cortico-recipient auditory midbrain neurons

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Senior Postdoctoral Research Scientist Johannes Dahmen from the King Group followed with a presentation, during which he discussed data suggesting that there is a pathway in the auditory system that is specialised for the detection of novel sounds, and that is separate from the main auditory pathway. "This specialisation for the detection of novel sounds may be independent from the cerebral cortex and arise from subcortical structures in the midbrain or even brainstem." (Dr Dahmen).

Cristina Blanco Duque: Sleep spindle quality as a measure of stability and synchrony within cortical networks

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The penultimate speaker was Wellcome Trust doctoral student Cristina Blanco Duque from the Vyazovskiy Group. She discussed her study of brain oscillations called sleep spindles, which are one of the most common forms of brain activity during sleep. "It is believed that these oscillations are important to protect sleep from external disruption and to consolidate memories during sleep. However, results regarding the functional role of spindles are not conclusive and are often inconsistent. One fundamental problem is that the traditional approaches to study sleep spindles use arbitrary parameters.  I am exploring new ways of defining, detecting and manipulating sleep spindles, which take into account their complex dynamics, and can help us to better understand their biological function, both in health and disease." (Cristina Blanco Duque).

sarah de val: athena swan in dpag

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Athena SWAN Academic Lead Associate Professor Sarah De Val was our last speaker of the day, reminding the Department's Researchers of the Athena SWAN initiatives in place and how these can help and support them. She also encouraged everyone to get involved with the newly established departmental working groups designed to enrich staff and student experiences at DPAG.