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Niko Tinbergen lecture

Stem cells, Dr. Jekyll or Mr. Hyde? The Niko Tinbergen lecture 2019 is delivered by Hans Clevers. Stem cells bring great promise, but are also at the basis of cancer, says Clevers. Before the main lecture, Ariane Briegel and Susana Chuva de Sousa Lopes tell the audience about their fields of research in two shorter lectures.

Stem cells are the basis of all life. In adult organs, old cells are constantly replaced through the division of stem cells. This renewal takes place at a particularly high rate in the skin, blood, bone marrow and intestinal lining. In other organs, stem cells become hyperactive after tissue damage, in an effort to repair the injury.

Stem cells have been a focus of great interest in recent years: they can be used to cure diseased tissues or to replace old, worn-out tissues. Scientists recently learned how to grow stem cells from healthy or diseased tissues in the laboratory to produce cultures in the form of mini-organs, known as organoids.

Many different applications for these organoids are currently being developed. As yet, they are not an alternative for organ transplants, but they certainly offer good prospects in the long term. They can play a role in regenerating organs by replacing the non-functioning tissue. Even if there were enough donors, regeneration with the patient’s own tissue is a much more natural and less invasive process than transplanting a whole organ. Another possible use is in repairing tissue damage. Researchers have found, for example, that injected mini-intestines (enteroids) can repair tissue damage caused by intestinal inflammations by acting rather like roving band-aids – at least in mice. Organoids are also highly valuable in fundamental research into genes and cell types. And finally, mini-organs are ideal as experimental tissue for testing drugs or procedures.Yet stem cells also have a ‘dark side’, being at the root of cancer as well. Knowing more about stem cells also gives us a better understanding of how certain forms of cancer develop. Stem cells: Dr. Jekyll or Mr. Hyde? Decide for yourself.

About the speaker

Hans Clevers is Professor of Molecular Genetics at University Medical Center Utrecht and Utrecht University. From June 2012 until June 2015 he was president of the Royal Netherlands Academy of Arts and Sciences (KNAW). Clevers is group leader at the Hubrecht Institute for Developmental Biology & Stem Cell Research and at Prinses Máxima Centrum for children oncologie.

Women who survive childhood cancer often fail to conceive, because chemotherapy can damage their eggs, all of which are present ass follicles in the ovaries from before the moment of birth. To prevent this damage, a major breakthrough has been the possibility to remove ovarian tissue before chemotherapy and preserve it by freezing, so it can be transplanted back later in life. This has led to over 150 successful pregnancies worldwide and several in the Netherlands. However, this treatment also comes with the risk of reintroducing cancer cells in patients. This risk is too great and alternatives are needed.

I am investigating ways to let immature egg cells from the preserved ovarian tissue mature in the laboratory, without the need transplant this tissue back into the patient. In this way, matured eggs could be used directly for in vitro fertilisation. Successful methods to induce the formation and maturation of young follicles in the laboratory have been a challenge for decades. However, recent developments in single-cell technologies, machine-learning algorithms and the use of biomaterials are providing the multidisciplinary context required to develop successful protocols. If these protocols can ultimately be taken to the patient, this will result in a paradigm shift and restored fertility. This would increase the chances of motherhood for cancer survivors, independent of age-related socio-economic or cancer (type)-related factors.

Alternatively, developing a reliable mini-ovary organoid system from patient-specific stem cells could lead to innovative reproductive technologies needed to conciliate the (reproductive) ageing of our modern society with the woman’s natural biological clock. Our approach aims to provide more effective personalized therapies for fertility preservation and contribute to the development of an in vitro mini-ovary organoid model to use in human reproductive toxicology and disease modelling.

About the speaker

Susana Chuva de Sousa Lopes is Professor of Developmental Biology at the department Anatomy and Embryology at Leiden University Medical Center.

Microbes are the most abundant organisms on earth and impact all aspects of our lives. But their small size makes them difficult to study, and we are just beginning to understand their cellular architecture: the cells contain multiple molecular machines that provide the basis of complex behaviors that are not dissimilar to behaviors seen in animals. We are following in the footsteps of the renowned Dutch behavioral scientist Nikolaas Tinbergen to study this behaviour on the microscale.

In order to gain insight into the nanomachines that underlie microbial behavior, we rely on high-powered modern microscopes that enable us to directly observe these structures inside the cells. This allows us to gain detailed insight into how microbes find their food sources and evade harmful toxins in the environment.

Many bacteria are motile - they either swim or crawl on surfaces by specialised cell appendages. But these movements are not random - they are directed by a sensory apparatus called the chemoreceptor array. This ‘bacterial nose’ allows the cells to 'smell' their chemical environment and enables them to seek out their most favorable conditions. Several pathogenic microbes utilize this system as the first step of host invasion.

To elucidate the structure and function of the molecular machines responsible for this behavior, we use a method called electron cryo-tomography. This allows the study of molecular machines in intact cells in three dimensions at macromolecular resolution. We aim to utilize this knowledge to find new ways of treating infections and design biosensors that will help us quickly detect certain diseases such as cancer.

About the speaker

Ariane Briegel is Professor of Ultrastructural biology at Leiden University. She is also co-director of NeCEN, the Netherlands Centre for Electron Nanoscopy.

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