News — Department of Pharmacology

Parrington group paper reveals role for TPC1 channels in mTORC1 activity

13 November 2024

New research published by the Parrington group help further understand the link between mTORC1 and endolysosomal ion channels, and reveal that TPC1 controls melanoma progression and represents a potential therapeutic target.

The illustration shows the upregulation of Gsto2, which encodes the glutathione S-transferase omega-2 (GSTO2) enzyme induced by the absence of TrkB signalling in the indirect pathway spiny projection neurons (iSPNs), the initially affected cells in Huntington’s disease, triggers an increase in dopamine, neuronal vulnerability, and motor dysfunction. The selective reduction of this protein activity in mice prevents dopamine and energy metabolism dysfunction, arresting the onset of motor symptoms.
Illustration from: Nat Metab (2024). https://doi.org/10.1038/s42255-024-01155-z

Discovery of key mechanism in Huntington’s Disease could pave the way for early detection and treatment

6 November 2024

New research published by the Minichiello group in Nature Metabolism has identified a key biochemical mechanism relevant to Huntington’s Disease, which opens the possibility of studying the disease before its clinical onset.

Figure 1. The development of tiny, soft and biocompatible batteries to power minimally invasive
biomedical devices is of critical importance. Here the authors present a microscale soft
rechargeable lithium-ion battery based on the surfactant-supported assembly of silk hydrogel
droplets. Scale bar: 400 μm. Image credit: Yujia Zhang

Batteries for miniature bio-integrated devices and robotics — here’s how to do it

4 November 2024

A new paper, published this week in Nature Chemical Engineering, highlights ground-breaking collaborative research between the Departments of Chemisty and Pharmacology to develop batteries for miniature bio-integrated devices. Featuring work carried out in the Lei Group, the research has led to the creation of a flexible soft lithim-ion battery constructed by assembling biocompatible hydrogel droplets.

ORCHID: all-Optical Reporting of CHloride Ion Driving force
(A) The novel approach combines a light-activated chloride channel with a genetically-encoded fluorescent voltage reporter. (B) Activation of the chloride channel with blue light drives the membrane potential (Vm; black trace) towards the reversal potential for chloride (ECl; green dashed line). The resulting Vm shift is measured via the genetically-encoded fluorescent voltage reporter, providing an estimate of the driving force for chloride (DFCl) that is effective across different ECl and Vm values

Akerman group study describes first new all-optical tool for quantifying inhibitory receptor driving forces

28 October 2024

A new paper from the Akerman group, published in the journal Nature Communications this week, explains the development of a new ‘ORCHID’ biosensor to measure the driving force acting on inhibitory receptors in the brain.

The connections between granule cells and Purkinje cells are extensive, with each granule cell synapsing on 400 Purkinje cells and each Purkinje cell receiving input from 50,000 granule cells in the mouse cerebellum. Therefore, by deleting Ntrk2 (the gene that encodes TrkB) in a subset of granule cells, researchers disrupted signalling in numerous Purkinje cells. In the schematic, intact synapses between granule cells and Purkinje cells are marked by red circles, while yellow circles reflect synapses through which communication is affected by the ablated BDNF-TrkB signalling.
Figure created in BioRender.

Minichiello group shows neurotrophin signalling dysfunction in a subset of cerebellar granule cells triggers ataxia

22 October 2024

A new study from the Minichiello group, published recently in the journal Biology, has shown that dysfunction in BDNF-TrkB signalling, restricted to a specific subset of cerebellar granule cells, is sufficient to generate ataxic symptoms

Department of Pharmacology research leads to FDA approval for new NPC treatment

26 September 2024

A Department of Pharmacology start-up company has received approval from the US Food and Drug Administration (FDA) for a new treatment for the rare lysosomal storage disorder Niemann-Pick Disease Type C (NPC) in both adults and children.

Collaboration in action - from a Pharmacology perspective

21 June 2024

As part of the Medical Sciences Division's series on industry collaboration, Pharmacology's Associate Professor Sri Vasudevan shares the important of networking at conferences and listening to a range of views as vital building blocks that can lead to effective commercial partnerships.

Pharmacology scientist awarded Royal Society of Chemistry prize

12 June 2024

Professor Angela Russell, who holds a joint appiontment with the Departments of Pharmacology and Chemistry, is one of four scientists from the University of Oxford who have won prizes from the Royal Society of Chemistry in recognition of brilliance in research and innovation. The awards are among the oldest and most prestigious research prizes in the world, having recognised excellence in the chemical sciences for more than 150 years.

New molecule found to suppress bacterial antibiotic resistance evolution

28 May 2024

Researchers in the Lanyon-Hogg group in the Department of Pharmacology, in collaboration with the Ineos Oxford Institute for antimicrobial research (IOI), have developed a new small molecule that can suppress the evolution of antibiotic resistance in bacteria and make resistant bacteria more susceptible to antibiotics. The findings have been published in the journal Chemical Science.

This image shows a graphical abstract of the new paper from the Akerman group, and illustrates how that the thalamic input received by a layer 4 excitatory cortical neuron in mice is influenced by the neuron’s embryonic progenitor type. Neurons derived from intermediate progenitors receive greater input from higher-order thalamus, which reflects their dendritic morphology and molecular mechanisms specified by the progenitors

New study from the Akerman group reveals the developmental origins of higher-order thalamocortical circuits in the brain

9 May 2024

A new paper by the Akerman Group is published in the journal Cell Reports this week and reveals how fine scale synaptic connectivity in the adult brain is shaped by events during embryonic development.

Co-crystallisation of structurally modified inositol polyphosphates and related carbohydrate-based surrogates with inositol 1,4,5 trisphosphate 3-kinase: left-hand panel shows the range of synthetically-modified ligands employed and right-hand panel shows an ensemble of co-crystal structures, showing also associated movements in an active site helix; centre panel shows the standard enzyme reaction.

Study defines novel kinase substrate tolerance and active-site plasticity

5 March 2024

A collaborative chemical biology study from the Potter Group, with the Gonzalez Group at CSIC Madrid, deepens understanding of an enzyme acting upon a crucial cellular messenger.

A group picture of the staff and students who showcased brain activities for pupils at Cheney School

Amazing Brain Festival at Cheney Secondary School

23 February 2024

Pharmacology staff and students contributed to a special afternoon of events last week to engage 200-300 students and families on the theme of the brain organised by their school ‘Rumble Museum’. A team of ten members of our department led by Dr Lizzie Burns developed five zones of activities to engage students with different aspects of neuroscience: memory, focus, build-a-brain, illusion and microscopy.

IntraBio trial makes progress on a potential treatment for Niemann-Pick C

13 February 2024

A successful Phase 3 clinical trial of N-acetyl-leucine (NALL) in the lysosomal storage disorder Niemann-Pick disease type C has been published this month in the New England Journal of Medicine.

Pharmacology highlights quality of its research at successful Research Symposium

15 January 2024

The Lei group in Pharmacology (left-right): Dr Tianyi Sun, Yue Ren, Yu He, Ming Lei, Alexey Lipov and Alex Grassam-Rowe

Lei group discovers catecholaminergic cardiomyocytes with potential endocrine function

29 November 2023

Featured in the Nature Communications Editor's Highlights at https://www.nature.com/ncomms/editorshighlights

New Smith/Refsum paper explores link between pollution and dementia

21 September 2023

A new study jointly published by Professors David Smith and Helga Refsum confirms that chronic exposure to air pollution in the elderly increases the risk of developing dementia a few years later.

Paolo Tammaro awarded the title of Professor of Pharmacology

14 September 2023

The University’s Vice-Chancellor has this week conferred the title of ‘Professor of Pharmacology’ on Paolo Tammaro.

New study from the Akerman group shows that synaptic inhibition changes dynamically to match brain state

4 September 2023

A new paper by the Akerman Group is published in the journal Neuron this week, and resolves a fundamental question in the field of neuroscience, by investigating how synaptic inhibition operates under undisturbed conditions. This new study demonstrates that GABA signaling in the brain is dynamic and adapts to control cortical functions depending on the state of the brain.

A still from the animation about Lysosomal Storage Diseases shows families at a conference to find out more about the disease that is affecting their family

New animations target families affected by Lysosomal Storage Diseases

28 July 2023

(right) Professor Annette Dolphin is presented with a commemorate plaque, by Professors David Smith and Peter Somogyi and Associate Professor Paolo Tammaro, following her Davd Smith Lecture and (left) Annette answers questions from students in the audience

Professor Annette Dolphin presents 17th David Smith Lecture in Pharmacology

14 June 2023

The latest David Smith Lecture in Anatomical Neuropharmacology was held in the Department on Wednesday 14 June 2023. Professor Annette Dolphin from the Department of Neuroscience, Physiology and Pharmacology at University College London presented a highly engaging lecture entitled "Drugs and trafficking: lessons from voltage-gated calcium channels".

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