Tag Archives: BSDB

Emilia Favuzzi: winner of the 2018 Beddington medal

The Beddington Medal is the BSDB’s major commendation to promising young biologists, awarded for the best PhD thesis in Developmental Biology defended in the year previous to the award. Rosa Beddington was one of the greatest talents and inspirational leaders in the field of developmental biology. Rosa made an enormous contribution to the field in general and to the BSDB in particular, so it seemed entirely appropriate that the Society should establish a lasting memorial to her. The design of the medal, mice on a stylised DNA helix, is from artwork by Rosa herself. We would like to congratulate the 2018 winner of the Beddington Medal, Emilia Favuzzi, and would like to take this opportunity to give a brief overview of her career and her PhD project that was awarded the Beddington medal.

Emilia started her studies in 2007 at the Sapienza University of Rome and was awarded a B.Sc. in Biological Sciences with highest marks in 2010. She stayed at the same university for her Master’s project which she performed in the laboratory of Sergio Nasi at the Institute of Molecular Biology and Pathology (CNR, Rome). She completed her M.Sc. in Neurobiology in 2011, again with highest marks. In 2011 she joined the group of Beatriz Rico at the Institute of Neuroscience in Alicante (Spain) and moved with that group to the Centre for Developmental Neurobiology at King’s College London in 2014 where she terminated her project work. Her PhD in Neuroscience was awarded in 2017 by the University Miguel Hernandez of Elche (Spain) also with summa cum laude. Since 2017 she is a postdoctoral associate in Gordon Fishell’s laboratory at the Broad Institute and Harvard Medical School.


Fig.1 Activity-dependent gating of parvalbumin interneuron function by the perineuronal net protein Brevican

During her PhD, Emilia worked on two projects which were both based on candidate and genome-wide screen approaches aiming to identify genes that were involved in GABAergic synapse formation. In one project, she investigated the role of perineuronal nets during the synaptic development of GABAergic interneurons. She discovered that the perineuronal net component Brevican is involved in the gating of parvalbumin interneurons by controlling their intrinsic properties as well as extrinsic input through excitatory synapses (Fig.1). This paper was published as a featured article in Neuron (2017). Emilia also took ownership within a parallel project, where she collaborated with another lab member to set up protocols to isolate different populations of interneurons and screen for genes involved in the specific synaptic targeting of cortical interneurons to the different compartments of pyramidal cells. This work led to the discovery of validated candidate genes involved in specific interneuron synapse formation, as shown via loss and gain of function approaches (Fig.2). The respective manuscript is in preparation and Emilia will be shared first author.

Her PhD supervisor Beatriz Rico said about her: “Emilia is a gift for a supervisor: she goes ahead of you, technically and conceptually and pushes you forward. She is brilliant, extremely motivated and creative person and resistant to any difficulties she has found during the development of her project. She never gave up and pursues her aims with an impressive efficiency. She is extremely independent and hard worker. She is fully committed to science, a dream for a supervisor.


Fig. 2 Highly selective cell-type specific programs regulate inhibitory synapse specification

Emilia receives the Beddington medal from Simon Bullock

Thesis abstract: Cell-type specific programs regulate the assembly and dynamics of cortical circuits

Understanding how neuronal connections are established and organized in functional networks during development is critical to understand brain function. In the mammalian cortex, GABAergic interneurons are characterized by a remarkable diversity of types and connectivity patterns. As such, they are uniquely suited to orchestrate functionally relevant circuit-specific roles and critically shape cortical function. Yet, how inhibitory circuit specificity is achieved during development is largely unknown. We revealed the transcriptional dynamics of different cortical interneurons during brain wiring and identified subtype-enriched synaptic molecules. Moreover, we showed that the functional connectivity of different interneurons relies on the cell-specific expression of such synaptic genes. Altogether, our results demonstrate that highly selective molecular programs emerging during development in cortical interneurons support their early wiring and underlie inhibitory circuit specificity. After their integration into canonical circuits, activity-dependent plasticity endows neurons with the flexibility required for adapting to sensory experience. Parvalbumin (PV+) interneurons have been shown to play a critical role in this process but the molecular mechanisms by which experience influences PV+ interneuron plasticity were poorly understood. We revealed how perineuronal net (PNN) proteins drive PV+ cell wiring as well as network adaptation to experience. We showed that the PNN protein Brevican simultaneously regulates the excitatory inputs and firing properties of PV+ interneurons by controlling the localization of AMPA receptors and potassium channels, respectively. We also showed that, by modulating Brevican levels, experience influences cellular and synaptic forms of plasticity in PV+ cells and this is required for normal cognitive function. These findings uncover a cell-specific molecular program through which a PNN protein dynamically gates PV+ interneuron function both during development and upon experience-dependent plasticity.


Papers by Emilia so far (* co-first authors)

Favuzzi E*, Deogracias R*, Marques-Smith A, Maeso P, Exposito-Alonso D, Balia M, Jezequel J, Kroon T, Hinojosa AJ, Rico B. Highly selective cell-type specific programs regulate structural synapse target specificity (manuscript in preparation) 

Favuzzi E, Marques-Smith A, Deogracias R, Winterflood CM, Sánchez-Aguilera A, Mantoan L, Maeso P, Fernandes C, Ewers H, Rico B. Activity-dependent gating of parvalbumin interneuron function by perineuronal net proteins. Neuron (2017)

Marques-Smith A*, Favuzzi E* & Rico B. Shaping Early Networks To Rule Mature Circuits: Little MiRs Go A Long Way. Neuron (preview), (2016)

Annibali D*, Whitfield JR*, Favuzzi E, Jauset T, Serrano E, Cuartas I, Redondo-Campos S, et al. Myc inhibition is effective against glioma and reveals a role for Myc in proficient mitosis. Nature Communications (2014)

Savino M, Annibali D, Carucci N, Favuzzi E, Cole MD, Evan GI, Soucek L, Nasi S. The Action Mechanism of the Myc Inhibitor Termed Omomyc May Give Clues on How to Target Myc for Cancer Therapy. PLoS One (2011)

Helen Weavers – Dennis Summerbell Awardee 2017

Following a generous donation, the BSDB has instituted the Dennis Summerbell Lecture, to be delivered at its annual Autumn Meeting by a junior researcher at either PhD or Post-doctoral level. The 2017 lecture awardee was Helen Weavers (School of Biochemistry, Faculty of Biomedical Sciences, University of Bristol) with her submitted abstract “Understanding the inflammatory response to tissue damage in Drosophila: a complex interplay of pro-inflammatory attractant signals, developmental priming and tissue cyto-protection”. Her award lecture was presented at the Autumn Meeting 2017, jointly organised by the BSDB together with the Swedish, Finish, Norwegian and Danish Societies of Developmental Biology, 25-27 October 2017 in Stockholm.

Helen’s work so far

After completing her PhD studies investigating Drosophila nephrogenesis in Helen Skaer’s lab in Cambridge, Helen moved to Bristol in 2013 to take up a 5 year, MRC-funded post-doc position between Paul Martin’s and Will Wood’s labs. Her first publication from this work (Weavers et al., 2016, Cell 165, 1658ff.), showed that Drosophila macrophages (haemocytes), must first be “primed” by engulfing at least one dead cell, before they are responsive to wound attractants. These findings are important because the majority of human pathologies are a consequence of too little or too much inflammation. What really excited the judges of the Denis Summberbell Lecture award was the work which had led to her most recent paper entitled “Systems Analysis of the Dynamic Inflammatory Response to Tissue Damage Reveals Spatiotemporal Properties of the Wound Attractant Gradient” (Weavers et al., 2016, Curr Biol 26, 1974ff.). This was a true multidisciplinary study, using a combined approach of mathematics and biology to analyse macrophage behaviours in response to tissue damage. Although the identity of the wound attractant signal/s are still not clear, this study was able to determine several of the characteristics of the attractant(s). Building on this strong platform of work, Helen is currently developing her own research towards understanding tissue protection/resilience in Drosophila and man, and this was an exciting novel element of her award lecture. In her talk, she described in a stunningly visual and understandable way how successful tissue repair relies not only on the host’s ability to mount an effective inflammatory response, but also on its ability to limit it. Her talk was a fabulous highlight and a shining example of high quality research by members of the BSDB.

Lecture abstract:

Understanding the inflammatory response to tissue damage in Drosophila: a complex interplay of pro-inflammatory attractant signals, developmental priming and tissue cyto-protection

Helen Weavers, Bristol, UK

An effective inflammatory response is pivotal to fight infection, clear debris and orchestrate the repair of injured tissues; however, inflammation must be tightly regulated since many human disease pathologies are a consequence of inflammation gone awry. Using a genetically tractable Drosophila model, I use precise genetic manipulation, live imaging and computational modelling to dissect the mechanisms that activate the inflammatory response to tissue damage and those that simultaneously protect the regenerating tissue from immunopathology. Upon tissue damage, immune cells (particularly neutrophils and macrophages) are recruited into the damaged area by damage signals (danger-associated molecular patterns, DAMPs) released from the injured tissue. In collaboration with computational biologists, we employ a sophisticated Bayesian statistical approach to uncover novel details of the pro-inflammatory wound attractants, by analysing the spatio-temporal behaviour of Drosophila immune cells as they respond to wounds. We show that the wound attractant is released by wound edge cells and spreads slowly through the tissue, at rates far slower than small molecule DAMPs such as ATP and H2O2. Strikingly, we also find that immune cells must be developmentally ‘primed’ by uptake of apoptotic corpses before they can respond to these damage attractant signals. Such corpse-induced priming is an example of “innate immune memory” and may serve to amplify the inflammatory response in situations involving excessive cell death – and otherwise limit an overzealous and damaging immune response. Indeed, whilst inflammation is clearly beneficial, toxic molecules (e.g. reactive oxygen species, ROS) generated by immune cells to fight infection, can also cause significant bystander damage to host tissue and delay repair – and may underpin chronic wound-healing pathologies in the clinic. To counter this, I find that wounded Drosophila tissue employs a complex network of cyto-protective pathways that promote tissue ‘resilience’, which both protect against ROS-induced damage and stimulate damage repair. Successful tissue repair, therefore, not only relies on the host’s ability to mount an effective inflammatory response, but also its ability to finely tune it and limit associated immunopathology.