Department of Pharmacology Seminar Series
Seminars will be held as usual in the Departmental Seminar Room at 12:30pm on Fridays in Full Term. After the talk there will be tea and cake and a chance to talk informally with the speaker.
If anyone wishes to have some time with any speaker before the talk, please contact Dr Paul Miller in advance.
Schedule for Michaelmas 2023
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Friday 13th October 2023: 12:30 pm – 1:30 pm |
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Third-generation approaches of antibody discovery and optimisation Dr Pietro Sormanni Department of Chemistry, University of Cambridge Abstract Antibodies play a crucial role as reagents in research and diagnostics, and are a key class of therapeutics. However, current technologies for antibody discovery and optimization are still subject to limitations. Established screening procedures are laborious and several hard-to-target antigens exist. Similarly, targeting predetermined epitopes and optimizing multiple biophysical traits simultaneously remains a challenge. I will discuss emerging technologies of computational antibody design, which enable the targeted design of antibodies for predetermined epitopes and the prediction and modulation of their developability potential, through the optimisation of multiple biophysical properties. Overall, it is increasingly possible to complement well-established in vivo (first generation) and in vitro (second generation) methods of antibody discovery with in silico (third generation) approaches, which provide time and cost-saving benefits and increased precision. These approaches are becoming sufficiently mature to be highly competitive for some applications, thus offering novel opportunities to streamline antibody development. Biography Pietro Sormanni is a University Research Fellow supported by the Royal Society. He leads a research group at the University of Cambridge that sits at the interface between computation and in vitro experiments. Their research is primarily focused on the development and validation of innovative technologies for computational antibody design, aimed at transforming the ways antibodies are currently discovered and optimised. Through numerous collaborations and industrial partnerships, their work has demonstrated the potential for computational approaches to complement established procedures and streamline antibody development, offering novel, time- and cost-effective alternatives. Prior to his current position, Pietro held a postdoctoral Borysiewicz Biomedical Sciences Fellowship from the University of Cambridge, obtained a PhD in Chemistry, and an MSc in Theoretical Physics. |
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Venue: Seminar Room (Level 2), Dept of Pharmacology |
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Refreshments in café (level 4) from 1.30 pm. |
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Recording: https://youtu.be/yJfTVV_lhmU?list=PLe8pAmQe8MdGWxOJlmff94P0J0rTn0LEK |
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Friday 20th October 2023: 12:30 pm – 1:30 pm |
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Exploiting nuclear envelope dysfunction in progeria to identify new therapeutic targets for ageing Dr Delphine Larrieu Department of Pharmacology, University of Cambridge Biography Dr Delphine Larrieu has been a Wellcome Trust Sir Henry Dale fellow and a Group Leader at the University of Cambridge since 2017. She initially set up her lab at the CIMR where she stayed for 5 years, and she was then appointed Assistant Professor in the Department of Pharmacology, where she relocated in October 2022. After working on tumour suppressor genes during her PhD at the University Grenoble Alpes (France), she developed a strong interest in the mechanisms linking nuclear envelope dysfunction with ageing and premature ageing syndromes (progerias) during her postdoctoral training in Steve Jackson's lab at the Gurdon Institute - Cambridge. Her work has focused on the identification of new markers and modulators of nuclear envelope integrity, to unravel the mechanisms underlying nuclear envelope dysfunction, improve our understanding of premature and physiological ageing and contribute to the development of novel therapies. She has developed pioneering approaches based on the principle of synthetic rescue and relying on cutting-edge genetic screening approaches, and identified novel, unexpected targets and cellular pathways that can reverse several age-related nuclear envelope phenotypes. Her current efforts are focused on characterising and expanding the number of targets that can be exploited therapeutically to extend health and lifespan in progeria syndromes as well as in ageing. Dr Larrieu is a co-founder of Adrestia Therapeutics – recently acquired by Insmed – a synthetic rescue company whose aim of restoring cellular balance in genetic diseases was directly inspired by her work. |
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Venue: Seminar Room (Level 2), Dept of Pharmacology |
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Refreshments in café (Level 4) from 1.30 pm |
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Recording: https://youtu.be/Tnqjc8G_BPg?list=PLe8pAmQe8MdGWxOJlmff94P0J0rTn0LEK |
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Friday 3rd November 2023 at 12:30 pm – 1:30 pm |
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GABA-A receptor subtypes controlling pain and itch Professor Hanns Ulrich Zeilhofer Department of Chemistry and Applied Bioscience Biography Hanns Ulrich Zeilhofer is Professor of Pharmacology at the University of Zurich (UZH) and the Swiss Federal Institute of Technology (ETH) Zurich. He is an MD by training and holds a board certification in Clinical Pharmacology. He did his postdoctoral training at the University of Erlangen, the Max-Planck Institute of Biophysical Chemistry and at ETH Zürich, before he joined UZH as professor of pharmacology. He has served as the director of the Institute of Pharmacology and Toxicology of the University of Zurich for 16 years and as a member of the research council of the Swiss National Science Foundation for 8 years. He is also a founding member of the Drug Discovery network Zurich (DDNZ). Currently, he serves as deputy dean of the Faculty of Medicine at UZH. His research has been supported by grants from the European Research Council (ERC), the Swiss National Science Foundation and the Wellcome Trust, among others. Current research projects concentrate on the cellular and molecular basis of nociceptive processing in the spinal dorsal horn. Central to his group’s research is the control of nociception by dorsal horn inhibitory neurotransmitters and inhibitory interneurons, which he and his team study on the molecular, cellular and circuit level. Molecular aspects include strategies to restore proper synaptic inhibition in pathological pain states. These projects have led to the identification a2 GABAA and a3 glycine receptors as potential targets in chronic pain conditions. To address the diversity of inhibitory dorsal horn neurons and their integration into local circuits and long-range projections his team has established a highly versatile toolbox of transgenic mouse lines and viruses suitable for conditional ablation, silencing and activation of genetically defined dorsal horn interneuron populations. |
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Venue: Seminar Room (Level 2), Dept of Pharmacology |
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Refreshments in café (Level 4) from 1.30 pm. |
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Recording: https://youtu.be/YB0UxYVGoHk?list=PLe8pAmQe8MdGWxOJlmff94P0J0rTn0LEK |
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Friday 10th November 2023 at 12:30 pm – 1:30 pm |
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Implications and molecular mechanisms of MOK, a new signaling kinase in neurodegenerative neuroinflammation Dr Cintia Roodveldt University of Seville Biography After graduating in Biotechnology (Universidad Nacional del Litoral, Argentina, 1999), Dr Roodveldt completed a PhD (2005, The Weizmann Institute of Science, Israel; Dan S. Tawfik’s lab) in the field of ‘enzyme evolution and emergence of new enzyme functions’. She then undertook a Postdoc at Prof. Chris M. Dobson’s lab (University of Cambridge, 2006-2009), investigating the ‘molecular mechanisms of Hsp70 chaperone system and a-synuclein aggregates linked to Parkinson’s disease’. In 2009 she joined David Pozo’s lab, a neuroimmunology lab, at CABIMER Center (Seville, Spain) and started a new line of research on the effect of protein aggregates in innate immunity. Since 2012, and having attained competitive tenure track positions (e.g. ‘Ramón y Cajal’ Researcher), they have led a research team studying the ‘mechanisms of microglial neuroinflammation triggered by a-synuclein aggregates and novel immunization strategies in Parkinson’. Her current research lines focus on the ‘identification of new signalling pathways and therapeutic targets related to immune dysregulation in neurodegenerative diseases, particularly ALS and Parkinson’. |
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Venue: Seminar Room (Level 2), Dept of Pharmacology |
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Refreshments in café (Level 4) from 1.30 pm. |
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Friday 17th November 2023 at 12:30 pm – 1:30 pm |
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PDRA talks Dr Stephanie Nestorow (Miller lab) Department of Pharmacology, University of Cambridge Biography Dr Nestorow completed their PhD at the University of Birmingham under the guidance of Professor Tim Dafforn focusing on using SMALPs for the polymer purification of difficult membrane proteins. During her PhD, their research focused on the development and characterisation of several novel polymers which were then utilised to study membrane proteins of agrochemical significance. During the PhD, they gained an aptitude for a variety of biochemical and biophysical techniques to investigate protein structure and function. Based on her experience purifying and characterising membrane proteins, they began my post-doc position within the Miller lab in December 2023. During their first year in the Miller lab, they worked on both GABA and glycine receptors. Her current research focuses on firstly, using Cryo-EM based structural techniques to decipher novel mechanisms of selective inhibition of Glycine receptors. Secondly, studying the structural basis of small molecule and toxin/antibody modulation of GABA receptors. Dr Anthony Keeble (Howarth lab) Controlling and combining signal activation for adhesion and receptor bridging Department of Pharmacology, University of Cambridge Biography Anthony did a PhD and post-doc with Professor Colin Kleanthous first at the University of East Anglia and then at the University of York where he applied biochemical and biophysical approaches to understand the mechanisms of inhibitor binding to protein toxins. Subsequently, Anthony used a combined structural, biochemical, and biophysical approach to understand immune receptor complex formation. Anthony used these studies to: (i) characterise the interactions of TRIM21, a novel intracellular IgG receptor, with antibodies at the Laboratory of Molecular Biology, Cambridge working with Dr Leo James; (ii) characterise the formation and mechanism of activation of the activating complexes of the classical (C1qrs) and lectin (MBL-MASP) pathways of complement at the Department of Respiratory Sciences, University of Leicester working with Professor Russell Wallis; (iii) characterise the mechanism of formation of receptors (FceRI and CD23) with the allergy related antibody IgE, as well as the influence of anti-IgE Fab binding at the Randall Division of Cell and Molecular Biophysics, King’s College London working with Professor Brian Sutton and Professor James McDonnell. Anthony is now working with Professor Mark Howarth within the Department of Pharmacology, University of Cambridge developing the novel protein coupling reagents: SpyTag/SpyCatcher, SnoopTag/SnoopCatcher, DogTag/DogCatcher, SnoopLigase, as well NeissLock that have a wide-range of applications: vaccines targeting COVID, malaria, and HIV; split chimeric antigen receptor-modified T cells, protein hydrogels, construction of antibody like molecules with controlled architectures, labelling bacterial outer membrane proteins to measure membrane dynamics, as well as selective labelling mammalian ion channels. |
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Venue: Seminar Room (Level 2), Dept of Pharmacology |
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Refreshment in café (Level 4) from 1.30 pm. |
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Friday 24th November 2023 at 4 pm – 5 pm |
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Engineering post-translational regulation of ion channels: basic mechanisms to translation Professor Henry Colecraft University of Columbia Biography Henry M. Colecraft, Ph.D. is the John C. Dalton Professor and Associate Vice Chair in the Department of Physiology and Cellular Biophysics at Columbia University Irving Medical Center. The Colecraft laboratory focuses on the molecular physiology of ion channel proteins that underlie signaling in nerve cells and the heart. His research group has contributed seminal advances to understanding molecular mechanisms underlying regulation of voltage-dependent Ca2+ and K+ channels by accessory subunits, posttranslational modifications, and signaling molecules. His group also studies how inherited mutations in ion channels lead to devastating diseases that span the cardiovascular, neurological, and respiratory systems, and seeking new therapies for them. |
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Recording: https://youtu.be/yJfTVV_lhmU?list=PLe8pAmQe8MdGWxOJlmff94P0J0rTn0LEK |
