At Roche's IHB, in vitro models and organ-on-a-chip models bring drug research closer to patients and also reduce testing on live animals.

Biologist engaged in the meeting point between human disease models, organoids and applied pharmaceutical research, Christoph Oberist works atInstitute of Human Biology (IHB) of Roche as Senior Research Associate in the Applied Organoid Technologies team. His research field is where experimental biology tries to overcome some of the limitations of traditional models: reconstructing systems in the laboratory that are ever closer to human physiology, better study diseases and make the path from the discovery of a potential drug to its preclinical evaluation more reliable.

In his work in Switzerland, Oberist takes care of the characterization of different organoid models, the development of experimental assays, their validation and subsequent transfer to research applications. This is a particularly significant position within the IHB, because it is located right on the border between biological innovation and industrial use: it is not enough to be able to build a sophisticated model, it is necessary to demonstrate that it is reproducible, measurable and sufficiently robust to become a useful tool for drug discovery and development.

It is in this context that technologies acquire particular significance “organ on a chip” used by Roche. Christoph in fact works on several models intended for the unit pRED, Pharma Research and Early Development, with the aim of better understanding the progression of diseases and the interactions between organism and drug. Among the projects discussed in the interview is the bioengineering of a stratified equivalent of the conjunctiva, consisting of polarized epithelial cells and differentiated goblet cells and designed to also acquire a component immune and neuronalThe aim is to have a model capable of contributing to the study of the mechanisms underlying the dry eye disease.

Behind this research, however, there is a broader issue, which now affects the entire sector of life sciencesHow much can new in vitro human models improve the ability to predict what will actually happen in the patient? Organoids and cultures derived from human samples allow us to observe biological phenomena with a degree of complexity that is difficult to achieve with conventional cell cultures and at the same time open the way to a more direct use of patient-derived material. For Oberist this evolution also has a precise ethical consequence: to contribute to the application of the principle of three Rs, that is Replace, Reduce, Refine, by progressively replacing, reducing, and refining the use of animals in research without diminishing scientific rigor.

The Institute of Human Biology represents the context in which this transformation is addressed with a deliberately transversal structure. The Applied Organoid Technologies group works on patient-derived cocultures and organoid models intended for industrial use, integrating its expertise with that of Roche's research and development ecosystem and with specialists in different pathological areas. The goal is not only to produce new models, but to transform the technologies developed by the IHB into assays usable in pharmaceutical development, more directly connecting bioengineering to precision medicine.

In a conversation with Thomas Clegg of the IHB, Christoph Oberist He describes this reality from the perspective of someone who works daily between the laboratory and the application. The sentence with which he summarizes his experience at the IHB,

“The work here is incredibly dynamic and you really feel that your contribution makes a real difference,”

It also conveys the character of a relatively young institution in which academia and industry are not conceived as two separate worlds, but as components of the same innovation process.

What emerges is a dialogue that goes beyond the single project: from organoids atorgan on a chip, from patient-derived models to the reduction of animal testing, Oberist explains how research can get ever closer to the real human biology and transform this knowledge into tools capable of making drug discovery more effective.

What inspired you to do what you do today?

My motivation stems primarily from the desire to help patients and have a positive and tangible impact on their lives by creating patient-based human disease models with the aim of improving the drug discovery process. I envision a future where we can use high-throughput, increasingly human-relevant tests that will not only accelerate research and discovery, but also enable the direct use of patient-derived samples. This will allow us to obtain more representative information about human biology and, at the same time, help progressively reduce the need for animal testing.

Why did you choose to join the Institute of Human Biology?

"When I decided to join the IHB, one of the main reasons was its reputation as an institution capable of making a truly significant impact. The IHB is at the forefront of in vitro model development and is truly a leading player both in terms of the technology itself and its practical application within industry. It is precisely this combination of technological development and the potential for concrete applications that was particularly important to me. This focus on translating research into reality was indeed a great attraction for me. Academia produces an enormous amount of groundbreaking discoveries and valuable research, but sometimes this work fails to complete the necessary process to become a final product capable of impacting society as a whole. The opportunity to contribute to the introduction and application of these new methods is therefore particularly exciting: they could have an impact not only locally, but, I firmly believe, on a global scale as well.”

What projects are you working on at IHB?

At the IHB, I work on several models using Roche's 'organ-on-a-chip' technology. The implementation of these devices in Roche's pRED (Pharma Research and Early Development) research and development unit will provide a window into deeper understanding of disease progression and the complex interactions between the body and drugs. The goal is to use these systems to observe and better understand biological phenomena directly relevant to pharmaceutical research. One of the most exciting projects we are currently working on involves the bioengineering of a stratified equivalent of the conjunctiva. This structure will feature a basal layer of polarized epithelial cells and a superficial layer of differentiated goblet cells. A particularly innovative element of the project is our attempt to make the tissue immune and neuronal competent as well, thus increasing the complexity and relevance of the model. This system, developed in collaboration with IHB scientists such as Marie Bannier, Mike Nikolaev, and Gray Camp and with researchers from pRED Ophthalmology such as Marco Künzli, Sarah Massot, and Hannah Kronabitter, will therefore allow us to more deeply study the mechanisms underlying dry eye disease.

What does it mean to you to be part of the institute's community?

"It's been a truly extraordinary experience so far, especially because the IHB is a relatively young institution. This translates into numerous unique opportunities and the chance to directly participate in the construction and development of new activities. Since we're still busy growing and structuring many aspects of the institution, the work here is extremely dynamic, and you really get the feeling that your contribution can make a tangible difference and influence the way things are developed. What truly sets the IHB apart, however, is its cross-disciplinary and highly collaborative nature: the level of collaboration is far superior to what is typically found in a purely academic or industrial environment. Here, we combine our expertise in human model development with the extraordinary depth of knowledge of our colleagues at pRED in various disease areas. This side-by-side work creates a very powerful synergy and allows the different skills to complement each other. I particularly appreciate the collaboration with the scientists at pRED: I can learn a great deal about the various diseases directly from the experts and, at the same time, teach them how to effectively use our in vitro organoid models. It's therefore a continuous and mutual exchange of knowledge, as well as an extremely rewarding working dynamic.”

What are your ambitions for the future? What excites you most?

IHB is a true innovation engine, and the field is evolving rapidly, progressively adopting these new technologies. Personally, my goal is to remain at the forefront of this development and adoption process. I hope to grow alongside the organoid field, helping to successfully implement a variety of models that can make the drug discovery process more efficient overall. At the same time, the increasing complexity of these systems will allow us to explore our biology as a species in ever greater depth and better understand its various mechanisms. If I can help Roche and the industry as a whole to live up to and advance the commitment of the three Rs—Replace, Reduce, Refine—while continuing to maintain and, hopefully, further improve current scientific standards, I would feel enormously proud to be able to concretely contribute to this process and its progressive diffusion within the industry.”

What do you appreciate about the Institute of Human Biology beyond its scientific work?

The Roche headquarters in Basel is truly a beating heart of science. There are numerous departments, each with its own expertise and specializations, which are easily accessible when needed. The ability to quickly contact colleagues, even within minutes, and directly tap into their expertise is extremely useful in our daily work. Everyone is very willing to collaborate across departments to achieve our shared goal of improving healthcare, and this openness makes the exchange of knowledge particularly effective. The headquarters itself is also extraordinary. The ability to host cutting-edge laboratories alongside beautiful, human-centric workspaces demonstrates how Roche cares not only about the quality of its research, but also about the people who work there every day.”

Here are three insights that might interest you:

Biology, computer science and engineering converge in Schällemätteli
How Roche accelerates research with human models and AI
SIP Basel Area: Architecture Becomes Innovation Infrastructure