Neurobiology of Ageing
The Schaefer lab studies the neuron-intrinsic and extrinsic mechanisms that govern age-associated brain changes. One of the major focuses of Schaefer's lab is the mechanisms that link peripheral impacts such as infection or inflammation with brain ageing. Infection is an inevitable part of human life that triggers both immune as well as behavioural responses. How these responses are connected is one of the key questions of Schaefer’s research program. The brain has a large population of resident and migratory immune cells that have the potential to affect brain function, both positively and negatively. For many years, studies of age-related neurodegeneration were focused primarily on neuron-intrinsic processes and largely ignored neuronal dependence on immune cells in the brain. Immune cells in the brain are represented by the innate macrophages-like cells in the CNS, the microglia, as well as by traversing peripheral B and T cells. During ageing and infectious diseases, these immune cells can impair brain functions by targeting brain cells in a fashion that resembles autoimmune diseases in the periphery and involves immune cell cytotoxicity. At the same time immune cells may support neuronal function and also “inform” neurons about the processes that take place at the organism “periphery”. How this information can be passed to neurons is not known. Recently we have discovered that microglia can adapt to specific neuronal phenotypes and that alteration in these adaptive processes may lead to aberrant microglial activation and neuronal death. We also found that microglia can control neuronal activity in a neuron-like fashion by using metabolic mediators commonly involved in immunomodulation in the organism periphery.
The overall aim of our research group is to understand the role of the immune-neuron interaction during brain ageing. We are particularly interested in understanding the epigenetic mechanism(s) of microglia adaptation to the neuronal environment and to peripheral impact as well as the mechanism(s) that drive microglia-mediated neuronal pathology. We are keen on defining the immune processes that could be used for treatment and possibly prevention of neurodegenerative diseases in humans.
Our research is focused on these main aims:
- How do early life experiences, such as peripheral infections, can shape the state of brain immunity and impact brain function later in life?
- Identify the mechanisms of suppressive microglia on neuronal activity and neuroinflammation
- Epigenetic mechanisms of microglia phenotypic plasticity and specification
- Epigenetic mechanisms of neuronal longevity
Applied methods and model organisms
- Transgenic mouse models
- in vitro cell systems
- Cell type-specific ribosome-bound RNA profiling (TRAP) and single cell/nuclei RNA sequencing
- Chromatin studies, Cut&Run, ATAC-seq, ChIP-sequencing analysis
- Mouse genetics and behavioral analysis
- Neuron Glia culture and activity assays (Axiom, Incucyte, Imaris)
- Immunostaining, brain clearance, in-situ, imaging analysis
- Molecular systems neuroscience, optogenetics, Ca-imaging in vivo.
- High resolution microscopy