Host: Dr. Henry McSorley

Venue: MSI Small Lecture Theatre, SLS

Abstract  

Cytokine-mediated regulation of immunity at mucosal sites is crucial in maintaining tolerance to the microbiota and innocuous antigens, but promoting beneficial responses against harmful pathogens. Work in my lab has focussed on how the crucial cytokine TGFβ regulates mucosal immune responses. Specifically, using animal models and human clinical samples, our studies have uncovered novel pathways by which integrins activate TGFβ to control innate and adaptive immunity in the intestine and lung, during health, inflammatory disease, and infection. Such work aims to identify novel therapeutic targets for immune-mediated diseases by targeting TGFβ activity in specific contexts and locations.  

Monday to Saturday: 12:00-17:00

Access

Cooper Gallery is located to the right side of the DJCAD buildings on Perth Road. The entrance is via double doors which face onto a car park.

The gallery is on two floors. Ground floor has ramped access. First floor is accessible by an internal lift and six steps with a handrail. Wheelchair access is via a stairclimber. Please email in advance if you require lift or stairclimber access.

First floor is also accessible via 24 steps. Two flights of 12 steps with handrails are separated by a landing.

Toilets

The ground floor has a wheelchair accessible toilet. The toilet is gender neutral.

Interpretation

Large print versions of the exhibition information handout are available, please ask our Guides. If you require alternative formats for material in exhibitions please email or ask our Guides.

View detailed accessibility information on AccessAble

Cooper Gallery
Duncan of Jordanstone College of Art & Design,
13 Perth Road,
Dundee,
DD1 4HT

                                                                               All Welcome

Host: Professor Alessio Ciulli 

Venue: Sir Kenneth and Lady Noreen Murray Seminar Room, CTIR 2.84 

Abstract:

 The landscape of cancer therapeutics has largely been confined to kinase catalytic domains. To expand the reach of therapeutics into new classes of therapeutic targets, we need to identify and validate specific mechanisms and pockets to enable drug discovery.  To enable this, we have developed a method called CysMAP for identifying druggable pockets in proteins of interest. Through screening of cysteine-variant libraries against tailored covalent small molecule libraries, CysMAP has successfully confirmed known pockets in KRAS and unveiled novel actionable ligand-bound conformations. Our approach, validated by structural analyses and functional screens in cancer cells, demonstrates the ability to distinguish compounds that selectively bind to specific protein variants. This technology holds promise for advancing drug discovery efforts against challenging targets like the RAS protein family, offering new personalized cancer treatment strategies.

 Bio:

 Moore van Tienen’s research is focused on developing novel therapeutic strategies in cancer by integrating functional genetic and chemoproteomic tools. He earned his PhD at the MRC Laboratory of Molecular Biology in Cambridge with Mariann Bienz, where he studied protein-protein interactions within the Wnt signaling pathway. He has extended his research as an EMBO postdoctoral fellow at the Broad Institute of MIT and Harvard, under mentorship of William Sellers, by devising methods to identify druggable pockets on oncogenic proteins. His efforts in developing new methods to systematically screen these targets against covalent compounds have uncovered potential novel binding conformations in RAS mutants, offering new avenues for the development of inhibitors.

Hosts: Dr Leeanne McGurk & Dr Raja Nirujogi

Venue: MSI Small Lecture Theatre, SLS

Summary: TDP-43 protein is ubiquitously deregulated in neurodegenerative diseases of aging, which often have a multifactorial nature and extrinsic stressors as a trigger/second hit. TDP-43 undergoes reversible nuclear condensation in stressed cells, including neurons. In the first part of my talk, I will introduce our recent study which characterised these TDP-43 condensates and identified determinants of their assembly and dissolution, in particular, the pivotal role of RNA. Furthermore, we found, using a novel confocal nanoscanning assay, that amyotrophic lateral sclerosis (ALS)-causative mutations alter TDP-43 condensation properties by changing its RNP affinity. Studies into the downstream effects of TDP-43 condensation revealed wide-spread splicing alterations in human motor neurons. Moreover, stress-induced splicing changes in TDP-43 targets were especially prominent and persisting for STMN2 RNA leading to rapid and persisting STMN2 protein depletion. In the second part of my talk, I will introduce a novel optogenetic platform for modelling aggregation pathology of ALS-causative C9ORF72 dipeptide repeat (DPR) proteins. Using this approach, we identified modifiers of DPR aggregation in cellular models and demonstrated that nuclear DPR aggregation causes TDP-43 condensation independent of stress response. These studies offer a model of the evolution of DPR pathology in ALS and shed light on the initial stages of disease development preceding the onset of cytoplasmic pathology. Overall, our results point to early pathological changes to TDP-43 in the nucleus and support therapeutic targeting of its condensation and stress response in ALS.

Bio: After graduating with an MSc degree in Genetics in 2008, I pursued a PhD in Biochemistry which I completed in 2012. During my PhD training, supported by an EMBO fellowship, I contributed to the generation and characterisation of a unique mouse model of a fatal neurodegenerative disease, amyotrophic lateral sclerosis (ALS); report on this mouse model published in J Biol Chem was selected as Paper of the Year. I continued to develop this stream of research during my postdoctoral training at Cardiff University (Prof Buchman’s lab), where I spearheaded several projects focussing on (dys)metabolism of ribonucleoprotein (RNP) granules in ALS. In 2015, these studies were supported by a 3-year fellowship from the Medical Research Foundation. In 2018, I was awarded a 4-year senior non-clinical fellowship from the MND Association and started my own group at the Medicines Discovery Institute, a newly established Cardiff University’s translational unit. During my time at the MDI, my research was supported by AMS Springboard award, the ISSF Translational Kick-Start award and funding from Welsh Government. I am the recipient of the ENCALS Young Investigator award 2020. In September 2021, I moved to SITraN, University of Sheffield, to continue studies into the molecular pathogenesis of ALS and related disorders within a world-leading centre for neurodegenerative disease research. In May 2022, I was awarded the UKRI Future Leaders Fellowship to establish a research programme entitled “RNA-protein complexes in health and disease and their therapeutic targeting”. The group is also funded by MNDA, BBSRC, MRC and MND Scotland as well as an MRC/AstraZeneca partnership grant and has a strong translational focus on developing RNA/RNP targeted small molecule therapeutics. Group webpage: https://www.ts-lab.co.uk/

Venue: MSI Small Lecture Theatre, SLS

Summary: TDP-43 protein is ubiquitously deregulated in neurodegenerative diseases of aging, which often have a multifactorial nature and extrinsic stressors as a trigger/second hit. TDP-43 undergoes reversible nuclear condensation in stressed cells, including neurons. In the first part of my talk, I will introduce our recent study which characterised these TDP-43 condensates and identified determinants of their assembly and dissolution, in particular, the pivotal role of RNA. Furthermore, we found, using a novel confocal nanoscanning assay, that amyotrophic lateral sclerosis (ALS)-causative mutations alter TDP-43 condensation properties by changing its RNP affinity. Studies into the downstream effects of TDP-43 condensation revealed wide-spread splicing alterations in human motor neurons. Moreover, stress-induced splicing changes in TDP-43 targets were especially prominent and persisting for STMN2 RNA leading to rapid and persisting STMN2 protein depletion. In the second part of my talk, I will introduce a novel optogenetic platform for modelling aggregation pathology of ALS-causative C9ORF72 dipeptide repeat (DPR) proteins. Using this approach, we identified modifiers of DPR aggregation in cellular models and demonstrated that nuclear DPR aggregation causes TDP-43 condensation independent of stress response. These studies offer a model of the evolution of DPR pathology in ALS and shed light on the initial stages of disease development preceding the onset of cytoplasmic pathology. Overall, our results point to early pathological changes to TDP-43 in the nucleus and support therapeutic targeting of its condensation and stress response in ALS.

Bio: After graduating with an MSc degree in Genetics in 2008, I pursued a PhD in Biochemistry which I completed in 2012. During my PhD training, supported by an EMBO fellowship, I contributed to the generation and characterisation of a unique mouse model of a fatal neurodegenerative disease, amyotrophic lateral sclerosis (ALS); report on this mouse model published in J Biol Chem was selected as Paper of the Year. I continued to develop this stream of research during my postdoctoral training at Cardiff University (Prof Buchman’s lab), where I spearheaded several projects focussing on (dys)metabolism of ribonucleoprotein (RNP) granules in ALS. In 2015, these studies were supported by a 3-year fellowship from the Medical Research Foundation. In 2018, I was awarded a 4-year senior non-clinical fellowship from the MND Association and started my own group at the Medicines Discovery Institute, a newly established Cardiff University’s translational unit. During my time at the MDI, my research was supported by AMS Springboard award, the ISSF Translational Kick-Start award and funding from Welsh Government. I am the recipient of the ENCALS Young Investigator award 2020. In September 2021, I moved to SITraN, University of Sheffield, to continue studies into the molecular pathogenesis of ALS and related disorders within a world-leading centre for neurodegenerative disease research. In May 2022, I was awarded the UKRI Future Leaders Fellowship to establish a research programme entitled “RNA-protein complexes in health and disease and their therapeutic targeting”. The group is also funded by MNDA, BBSRC, MRC and MND Scotland as well as an MRC/AstraZeneca partnership grant and has a strong translational focus on developing RNA/RNP targeted small molecule therapeutics. Group webpage: https://www.ts-lab.co.uk/