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IHB faces of innovation: Bruno Gjeta

Published November 22, 2024

The success of IHB owes much to the wonderful and inspiring people who work in its labs. We are featuring Bruno Gjeta, who is the first student to receive his PhD at IHB and works in the Developmental Systems and Computational Biology team.

“Since childhood, I have always been curious about the complexity of the realities around me.”

Bruno Gjeta
Research Fellow
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1. What inspired you to do what you do today?

Since childhood, I have always been curious about the complexity of the realities around me. I wondered how things work and dreamt of being a scientist. These feelings got reinforced during adolescence after my Retinitis Pigmentosa diagnosis. From then on I aspired to fuse my curiosity with the purpose of providing therapeutic solutions to patients who, just like me, did not have any. This initiated me to biotechnology in my early 20s and eventually led me to where I am today.

2. Why did you join IHB?

IHB is an interdisciplinary entity which strives at improving our understanding of human biology as well as disease phenotypes by leveraging innovative technologies. I wanted to join IHB for the opportunity to collaborate and learn from so many great scientists and together advance fundamental research as well as translational solutions. As a personal achievement, I am proud to say that I was the first PhD graduate of both IHB and Gray Camp’s lab.

3. What project(s) are you working on at IHB?

My research focused on investigating human disease progression and therapeutic potential using single-cell technologies and organoid models. The goal is to identify key principles that drive the progression of a particular disease or undesired effect of a treatment. In this endeavor, we aim at gaining a set of more specific molecular features that could help detect the disease state early on as well as understanding which levers we can pull when trying to prevent progression into harmful phenotypes. The hope is that this knowledge could translate into therapeutic targets in areas with as yet unmet clinical needs.

Excerpt of Figure 3 from Recaldin et al. 2024 Nature: Human intestinal immuno-organoids (IIOs) recapitulate clinically manifested intestinal inflammation associated with T cell-bispecifics (TCB). In f, Integrated UMAP embedding (left) and proportional distribution (right) of gut-derived immune cells from IIO model, coloured by treatment and profiling time. g, Barplot showing significantly enriched Gene Ontology biological processes for activated cell states (top) and heatmap showing average expression profiles of corresponding associated genes (bottom). h, Dotplot summarizing the expression pattern of representative genes involved in proliferation, signalling and cytotoxicity in activated T cell populations, as captured by scRNA-seq snapshots at different time points and under various treatment conditions. i, Flow cytometry plots visualizing expression of TNF, IFNγ, Gzmb and Ki67 across different time points within CD4+ and CD8+ TRM cells isolated from IIO cultures. Representative of five biologically independent experiments. Scale bars, 1 mm

4. What does being a part of the IHB community mean to you?

My expertise in human biology and computational analysis contribute to identifying, understanding and communicating scientific insights that help push IHB’s collaborative projects. In one recent work, a collaboration between three different teams at IHB, we described how interactions among tissue-resident gut immune cell populations contribute to cytotoxicity in response to cancer biologics. We identified and described specific contributors to the cytotoxic activation and validated strategies to mitigate it which provide an inroad to manage clinical side effects when developing new therapeutics.

5. What are your future ambitions? What are you most excited about?

My time at IHB has been valuable in helping me understand what I enjoy and where I can grow further. This will guide me in pursuing opportunities that are more aligned with my long-term goals.

Excerpt of Figure 4 from Recaldin et al. 2024 Nature: Transcriptomic analyses elucidate the immune dynamics underlying TCB-mediated inflammation and help identify mitigation strategies. In g, In silico perturbation analysis simulating the loss (KO) of TNF in the IIO model treated with EpCAM TCB. Plots show predicted perturbation-induced state transition (top) and enrichment (bottom). h, Schematic of experiments performed to inhibit TNF signalling and cell migration. Organoid cartoon adapted with permission from ref. 60. i, Representative images showing induction of caspase 3/7 signal within IIO co-cultures 40 h following supplementation with either a non-targeting control TCB or 5 ng ml−1 EpCAM TCB, with or without 10 µM ROCKi or a TNF blocking antibody. j, Bi-hourly quantification of caspase 3/7 signal in IIO cultures; top, comparison of EpCAM TCB + isotype with EpCAM TCB + adalimumab; bottom, comparison of EpCAM TCB + vehicle with EpCAM TCB + ROCKi. Data represent mean and standard deviation (grey shading) of three independent biological replicates; two-tailed unpaired t-test of the area under the curve generated for each condition. Scale bar, 200 µm. FC, fold change.

6. What do you enjoy about IHB beyond the science?

The IHB community is quite diverse with people coming from lots of different countries and backgrounds. This opens the door for very interesting and fun interactions over a beer by the Rhein.

Reference:

Recaldin T*, Steinacher L*, Gjeta B*, Harter MF*, …, Cabon L^, Camp JG^, Gjvorevski N^ (2024) Human organoids with an autologous tissue-resident immune compartment. Nature.

*lead authors, ^senior corresponding authors

DOI: 10.1038/s41586-024-07791-5

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