PhD project title: Mechanobiology of hippocampal neurogenesis

Irem’s PhD research is focused on understanding how mechanical signals and mechanotransduction-associated molecular pathways in neural stem cells can direct cell fate and their differentiation into mature neurons or glial cells. In particular, she is focused on the role of Piezo1 channels in modulating neurogenesis in the dentate gyrus of the hippocampus. To explore this hypothesis, Irem has developed a novel 3D organotypic brain slice culture model to image and track the effects of pharmacological activators and inhibitors of mechanosensitive ion channels on stem cell differentiation into mature neurons or glial cell types. The aim is to identify potential novel drug targets to enhance neurogenesis in the ageing brain. 

PhD project title: Impact of stress and breast cancer on the proteome of brain synapses

Walla’s PhD research focused on characterising the proteomic changes in brain synapses caused by mammary tumour burden (i.e. breast cancer). In particular, she is interested in comparing and contrasting changes in synaptic plasticity-associated proteins in key brain regions such as the hippocampus, prefrontal cortex, hypothalamus and cerebellum. Walla has discovered that mammary tumour burden impacts the hippocampus and prefrontal cortex brain synapses far more than the cerebellum, for example. This may help to explain why non-CNS cancers lead to cognitive impairment, even before chemotherapy treatments have been initiated.

PhD project title: Impact of social isolation on cognition and mental health at different ages across the lifecourse

Daniela’s PhD research focused on the impact of social isolation on the neuroinflammatory state of the brain. In particular, she has found that middle-aged adults may be more susceptible to the detrimental cognitive effects of social isolation compared to adolescents. Indeed, younger subjects appear to demonstrate resilience to the psychological stress of isolation. Middle-age adults, on the other hand, display greater deficits in spatial memory and exhibit depressive-like behaviours after a period of social isolation compared to younger subjects. Therefore, Daniela’s research suggests that social isolation, such as that experienced by many people during the recent global pandemic, may differentially impact the cognitive and mental health of young, middle-aged and older adults.

Project title: Mechanobiology of the Alzheimer’s disease brain

Ana’s research focused on how Alzheimer’s disease pathology impacts mechanotransduction-related proteins in cortical and hippocampal neurons of the TgF344-AD model. She also investigated ageing- and Alzheimer’s disease-associated changes to perineuronal net expression and extracellular matrix (ECM) molecules in brain regions badly affected by high densities of amyloid plaques. Her work brings us closer to a better understanding of the myriad changes in ageing brain tissue that most likely contribute to the maladaptive changes in synaptic plasticity associated with neurodegenerative disorders, such as Alzheimer’s disease.

Ana is now a Postdoctoral Research Associate in the Francis Crick Institute (London). 

Project title: Impact of long-term environmental enrichment on the ageing brain

Lorena’s research focused on how long-term environmental enrichment can change the proteome of cortical synapses and neighbouring astrocytes. Daily access to cognitive stimulants such as exercise, a large social network, and a safe and enjoyable living situation can positively shape the brain and protect against neurodegenerative and mental health disorders. Lorena investigated the molecular mechanisms responsible for promoting cognitive resilience in middle age using mass spectrometry-based proteomic analysis of cortical synapses and astrocytes, the predominant glial cell type in the brain.

Lorena transitioned to a Research Fellow position in the School of Psychology, University of Nottingham, where she studied the effects of psychedelic drugs on brain and behaviour.

PhD project title: Mechanobiology of the ageing and degenerating brain

Chloe’s PhD research focused on how and why the mechanical properties of the brain change with age and in response to Alzheimer’s disease pathology. In particular, she developed novel and sophisticated methods to map the mechanical properties of the hippocampus at high spatial resolution using atomic force microscopy and ex vivo brain slices. She discovered that the physical stiffness of the dentate gyrus increases from youth to old age. Interestingly, brain tissue of both the CA1 and dentate gyrus regions become much softer and lose their mechanical integrity in Alzheimer’s disease and this coincides with elevated astrogliosis due to heavy amyloid plaque burden in the hippocampus.

Chloe is now a Postdoctoral Research Fellow at the Universitätsmedizin der Johannes Gutenberg-Universität Mainz (Germany). 

PhD project title: Cancer-related stress and cognitive impairment

Myrthe’s PhD research focused on understanding the impact of non-CNS tumour growth (i.e. breast cancer) on brain physiology. In particular, she was interested in elucidating the molecular mechanisms of ‘cancer-related cognitive impairment’ and how the psychological stress of a cancer diagnosis affects learning and memory formation. She discovered that mammary tumour growth can cause dysregulation of the immune system (i.e. T lymphocyte numbers) and induces neuroinflammation in the prefrontal cortex. Moreover, breast cancer leads to proteomic changes in the hippocampus that suggest the observed deficits in memory formation may be caused by oxidative stress and maladaptive changes in synaptic plasticity.

Myrthe is now researching novel immunotherapeutic strategies to treat brain tumours and is currently an FWO Postdoctoral Fellow in VUB (Belgium).

PhD project title: Investigating the role of the mechanosensitive channel, Piezo1, in the CNS

Maria’s PhD research focused on understanding the role of mechanically-gated ion channels in neuroinflammatory disorders of the central nervous system, particularly multiple sclerosis and Alzheimer’s disease. She discovered that reactive astrocytes engulfing amyloid plaques in the ageing brain express higher levels of Piezo1 channels and that pharmacologically increasing their opening probability decreases release of proinflammatory cytokines. Interestingly, this suggests that upregulation of Piezo1 channels may be neuroprotective in the Alzheimer’s disease brain and could represent a novel drug target for enhancing neuroprotection.

Maria is now researching the role of mechanoreceptors in tumour progression and is currently an MSCA fellow in CNIO (Spain).