Lectures of The COINS 2023

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Dr. Martin Howard

Dr. Martin Howard will present at Ecology Day, April 25th 10:15

We are studying the mechanistic basis of epigenetic regulation in the Polycomb system, a vital epigenetic silencing pathway that is widely conserved from flies to plants to humans. We use the process of vernalization in plants in our experiments, which involves the memory of winter cold to permit flowering only when winter has passed via quantitative epigenetic silencing of the floral repressor FLC.

Utilising this system has numerous advantages, including slow dynamics and the ability to read out mitotic heritability of expression states through clonal cell files in the roots. Using mathematical modelling and experiments (including ChIP and fluorescent reporter imaging), we have shown that FLC cold-induced silencing is essentially an all-or-nothing (bistable) digital process. The quantitative nature of vernalization is generated by digital chromatin-mediated FLC silencing in a subpopulation of cells whose number increases with the duration of a cold. We have further shown that Polycomb-based epigenetic memory is indeed stored locally in the chromatin (in cis) via a dual fluorescent labelling approach. I will also discuss the mechanisms by which long-term fluctuating temperature signals are sensed before being converted into digital chromatin states for long-term memory storage.

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Dr. Anne Parle-McDermott

Dr. Anne Parle-McDermott will present at Ecology Day, April 25th 15:00

This seminar will describe both a career and a research interest journey. Having worked with nucleic acids for over 25 years it has been interesting for Anne Parle-McDermott to apply her knowledge and expertise in molecular genetics to a range of research questions.

The main interest of her group has been to understand the role of the essential B vitamin, folate, for human health with a particular interest in the prevention of Neural Tube Defects. Folate is a key supplier of the One Carbon Metabolism (OCM) pathway which is required for numerous essential cellular reactions including the methylation of DNA / proteins and supplying the one carbons necessary for DNA synthesis.

More recently, Parle-McDermott’s group has branched out to the examination of environmental DNA which is the DNA that is left behind by a given species within its habitat. They were the first to apply CRISPR-Cas technology for single-species detection from environmental DNA enabling them to further develop this approach to biosensors to detect any target species. Having two quite different strands to her research has proven to be fruitful and interesting with similar molecular techniques and know-how underpinning both aspects and illustrating the value of addressing a diverse range of research questions.

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Dr. Thomas Oertner

Dr. Thomas Oertner will present at Neurosciences Day, April 26th 10:15

Any time we learn something new, the new information is stored in our brain as lasting changes in connectivity between many neurons. Some of this stored information we can access at will (declarative memory), and some of it becomes part of our personality without us even knowing. The synaptic theory of memory is plausible, but actually pinpointing the neurons or synapses that store a particular memory in a living animal has proven quite difficult: The number of synaptic connections in a single brain is astronomical (1015), and these synapses are densely packed and wired in 3D, not nicely spread out on a microscopy slide.

Nevertheless, neurobiologists came up with sophisticated experiments to identify and modulate neurons that were highly active during learning. Most studies focused on two brain areas: the hippocampus as a relay station for spatial and contextual information, and the amygdala, responsible for the emotional content (valence) of specific memories.

As Thomas Oertner will discuss, recent progress has been largely driven by the advent of chemo- and optogenetics, as well as microscopy techniques to monitor and modulate the activity of specific neuronal populations. He will also explain some of the challenges and limitations of these approaches, e.g. the use of immediate early genes to tag the most active neurons in a specific time window.

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Dr. Nathalie Rieser

Dr. Nathalie Rieser will present at Neurosciences Day, April 26th 11:45

Mental illness is among the greatest public health challenges and there is an urgent need for effective treatment options. Psychedelics are gaining increasing interest in the treatment of psychiatric disorders such as depression and substance use disorders. In this climate, it is necessary to explore the underlying mechanisms of action of these substances in more detail.

In this presentation, emerging methods and clinical implications of psychedelic research will be outlined and psychedelic-induced altered brain activity will be discussed.

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Dr. Audrey Lapinaite

Dr. Audrey Lapinaite will present at Biomedicine Day, April 27th 10:15

Programmable DNA base editors are emerging state-of-the-art tools for precision medicine. Here Audrey Lapinaite will present a cryo-EM structure of ABE8e trapped in a substrate-bound state showing how the deaminase domain (TadA) contacts the non-target strand of double-stranded DNA exposed in the Cas9 – R-loop state. The enzyme kinetics of four generations of evolved ABEs show how accelerated DNA deamination governs on- and off-target adenine base-editing.

Mutations in evolved TadA that accelerate base editing cluster near the TadA-DNA interaction interface and explain the fast kinetics of ABE8e. Structure-guided alteration of these contacts can now direct the design of more specific base editors for cell-based genome editing biomedical applications.

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Dr. Piotr Trzonkowski

Dr. Piotr Trzonkowski will present at Biomedicine Day, April 27th 15:00

T regulatory cells (Tregs) are considered a viable option in immunosuppressive treatment in the clinic. The first promising clinical experiments and trials with clinical-grade Tregs cultured as advanced therapy medicinal product (ATMP) are completed already.

In our centre, the drug has been tested in graft versus host disease, type 1 diabetes and multiple sclerosis. We will present the path from preclinical studies to the results of clinical trials and the regulatory path towards the marketing authorisation of this cellular drug. In vivo results will be supported with in vitro and animal models showing the activity of Tregs in auto- and allogeneic settings.