Host: Dr Henry McSorley Dr Andy Howden & Dr Linda Sinclair  

Venue: The Murray Room CTIR 2.84 

Biosketch 

Roger Geiger obtained his Master’s and PhD degrees from ETH Zürich. During his PhD studies with Ari Helenius, Roger investigated how non-enveloped viruses penetrate the host cell membrane. He then joined the laboratory of Antonio Lanzavecchia at the Institute for Research in Biomedicine (IRB) to study metabolic regulations of T cell responses. In 2016, Roger joined the research group of Matthias Mann at the Max Planck Institute of Biochemistry in Munich and received training in mass spectrometry-based proteomics. In 2017, Roger started his research group at the IRB focusing on immune responses to tumours using systems biology approaches. 

Abstract 

I look forward to presenting an overview of our research. In the first segment of my talk, I will present a study on the capability of naïve T cells to rapidly respond to antigens. Utilizing a mass spectrometry-based pulsed SILAC approach, we assessed protein synthesis rates in primary human T cells and estimated mRNA copy numbers through RNA-Seq data. This integrative analysis unveiled that resting T cells maintain ready-to-act molecular machinery, such as idle ribosomes and inactive glycolytic enzymes, allowing a swift response to external stimuli. 

The second part of my presentation will focus on our investigation into the potentiation of anti-tumour T cell responses via L-arginine. We discovered that oral administration of L-arginine increased the number of tumour-infiltrating T cells, acting synergistically with PD-L1 blockade to induce tumour regression. Due to practical limitations with high-dose L-arginine administration, we developed a novel approach: an engineered probiotic bacterium capable of converting ammonia—a common metabolic waste product in tumours—into L-arginine. This strategy led to remarkable synergistic effects with PD-L1 blockade in tumour clearance, highlighting the potential of therapeutic bacteria in modulating tumour metabolism to boost anti-tumour immunity. 

In the final section, I will discuss a project in which we analyzed proteomes of immune cells isolated from tumours of HCC patients. We discovered that chronically stimulated T cells in tumours upregulate the protein AFAP1L2. Genetic ablation of Afap1l2 in murine T cells enhanced their anti-tumour activity in preclinical tumour models 

Host: Professor Jason Swedlow

Venue: MSI Small Lecture Theatre, SLS

In-Person Discovery Seminar

This seminar is fully funded by external sources.

Cells must rapidly regulate distinct peripheral projections autonomously within the same cytoplasm. Transcription alone cannot explain such regulation. mRNA transport and local translation are attractive mechanism to autonomously regulate the peripheral cytoplasm, independently of the cell nucleus. We are studying these processes in the most extremely polarised cells within an intact tissue, namely glia and neurones. Glial cells, like neurones, have long cytoplasmic projections that contact many other glial cells and multiple different neurones. These projections are known to be rapidly remodelled in response to neuronal activity and signalling events, crucial for nervous system function. We are using two systems: developing Drosophila larval motoneurons and surrounding glia undergoing subtle remodelling; and adult brain circadian master-clock PDF neurones and astrocytes undergoing dramatic daily light/dark-dependent cytoplasmic extension/retraction. We have already identified many examples of disease-linked localised mRNAs with remodelling functions in glia and neurons of both systems, encoding membrane/cytoskeletal regulators or junctional proteins and mRNA binding proteins required. Many of these transcripts are required for correct glial-neuron connections, neuronal plasticity and behaviour. We are using diverse interdisciplinary methodologies, including spatial transcriptomics, live super-resolution and single-molecule imaging. Our work has not only uncovered novel general principles of how the periphery of cells are regulated autonomously of the cell nucleus. It also provides candidate explanations for various poorly understood glial/neuronal-based diseases.