Professor Claudio Alonso
Neurogenetics Lab
My laboratory investigates the molecular mechanisms controlling the development and function of the nervous system (/lifesci/alonsolab/index).
At the fundamental level, neuronal mechanisms are evolutionarily conserved all the way from insects to mammals, making it possible to use simple organisms to deduce the main principles of brain organisation and function. Building on this notion, we use the fruit fly Drosophila melanogaster as a model system, exploiting its excellent genetic, cellular and transcriptomic resources, and the detailed understanding of neural development, neural morphology and behaviour available for this organism.
Recent work in my lab has established that specific genes, encoding transcriptional regulators (Hox genes) or small regulatory non-coding RNAs (microRNAs) can have specific effects on behaviour (Picao-Osorio et al. 2015 Science; Picao-Osorio et al. 2017 Genetics; Issa et al 2019 Current Biology; Klann et al 2021 J. Neurosci.; Issa at el 2022 PNAS; Menzies et al 2024 eLife); we also showed that microRNAs can affect the development of complex morphologies involved in behavioural control (Kaschula, et al. 2018 Development). Further work has examined how neurons acquire their unique morphological and functional features, identifying key genes and mechanisms that are necessary for normal neural function (Thomsen, et al. 2010 Development; Rogulja-Ortmann et al. 2014 Development; Costa et al. 2014 Developmental Biology; Vallejos-Baier et al. 2017 J. Mol. Biol.). Interestingly, some of the Drosophila genes that we study are also present in humans where they have been associated to neural disease enabling us to use Drosophila as a model of neural disease (Verma et al. – in prep.).
New projects could investigate the roles played by specific genes in the development and function of the nervous system in the context of both, health and neural disease. Conversely, new projects might be focused on a specific behaviour or physiological question and explore its molecular cellular basis. The results of our work should contribute to the understanding of the genetic basis of brain development and physiology, linking molecular mechanism to behaviour.
We would be particularly interested in student-led projects, but we can envisage different styles of projects, for instance, we could:
• Design a project that is centred on a particular behaviour, focusing on sensory-motor aspects, and investigate the molecular cellular processes underlying the behaviour.
• Plan a project that is centred on particular genes (Hox genes, microRNAs) or processes (epigenetics, neural activity, neural communication) and establish how these genes/processes regulate the biology of neurons during the formation and maintenance of neural circuits.
• Model a neural condition in Drosophila – we have recently done this for Huntington Disease – and examine the molecular/cellular basis of the condition, as well as its impact on neural physiology and behaviour seeking to establish novel ways of treating such condition.
We will then address our questions through the combination of a wide spectrum of methodologies, including: molecular biology, transcriptomics, connectomics, genetics, cell and developmental biology, optogenetics, optical imaging of neural function, quantitative behavioural approaches and advanced microscopy.
As said above, we will aim to accommodate the individual interests and skills of the student so that they develop an exciting and successful ‘bespoke’ project with full commitment and enthusiasm. We would welcome the implementation of an evolutionary and/or comparative approach to our research questions.
The lab is driven by an international group of talented Post-docs, PhD students and Technicians with diverse backgrounds and interests that range from molecular biology, development, neurophysiology and behaviour. The common denominator across all lab members is our strong commitment to understand how gene regulatory programmes control the formation and function of the brain.
Keywords: Neuron, Neurodegeneration, Neural disease, RNA, microRNAs (miRNAs), Drosophila, Behaviour, Sensory biology, Motor Control, Sensory-motor control, Movement