He can easily talk about it for an hour and a half, or longer if you’d let him: the magic of aneuploid cell division. This is the research field of Floris Foijer, a biologist who specializes in ageing, although his research generally focuses on how aneuploidy develops, what it entails and most importantly, the implications of aneuploidy for cells, tissues and entire organisms.
Aneuploidy is a change in cells whereby the nucleus has one or more chromosomes too many or too few. It occurs during cell division if a chromosome pair that has replicated itself does not divide equally over two daughter cells. It is a mistake that cancer cells often make, and possibly ageing cells too.
Foijer’s team consists of six people, all of whom have their own area in the research project as a whole. The research project revolves around mouse models, in which the researchers can activate aneuploidy in tissues in order to observe the interaction with ageing and cancer cells.
Seventy percent of cancer patients have cancer cells with this genomic mutation. These cells are the focus of Foijer’s research. ‘Current practice is to attack the abnormal, fast-dividing cancer cells with chemotherapy. This damages and kills the cancerous cells, but unfortunately, also hair and blood cells. In addition, it doesn’t always kill them all, and the remaining cells can cause the cancer to return, says Foijer. ‘If we could come up with something that would only kill the fast-dividing cells, we might be able to treat this seventy percent more effectively.’
But there is still a long way to go, admits Foijer. At the moment, he is developing defined aneuploid tumours in mouse models with mutations to find out what the mutant cells have in common. ‘These models have to be very alike’, explains Foijer. ‘This allows us to identify the chromosomes in which aneuploidy begins, which genes stimulate aneuploid cancer and exactly what they have in common.’
He discovered, for instance, that certain chromosomes in many of the tumours had disappeared or multiplied. ‘Aneuploidy accelerates cancer’, says Foijer, ‘but it does not necessarily cause it, as was previously thought.’ He hopes that his research will eventually lead to better treatment. ‘Greater understanding of the consequences of aneuploidy is the first step’, says Foijer.
The world of stem cell researcher Eugene Berezikov and his team consists mainly of worms. Flatworms, the Macrostomum lignano model to be more precise, which he uses for his research into stem cells, regeneration and ageing.
He doesn’t actually spend much time in the lab these days. He leaves this to his team, which consists of five postdoc researchers, two PhD students and two technicians. Berezikov himself analyses the data at his computer, holds weekly consultations with his team and attends the Friday ERIBA meeting with all the other researchers in the institute.
Regenerating broken tissue
Berezikov is trying to find out how his worms can repair (or regenerate) broken or lost tissue. If you cut off a worm’s tail, it grows back. Berezikov is studying the stem cells to find out how this works. ‘We want to understand how stem cells work and then translate the information for use in humans. If worms can do it, perhaps people can too’, says Berezikov.
Not that his findings can be directly transposed onto human beings, but they might help us to design better, more specific experiments for humans. Experiments that will help us to understand and perhaps even treat diseases relating to the ageing process.
Berezikov is keen to understand exactly how ageing affects the functioning of stem cells. ‘Knowing this will help us to develop stem cell-related treatment methods.’ He hopes that his research will provide conclusive evidence showing whether stem cells regenerate less effectively as they get older. ‘We need to know whether this really is the case and if so, which molecular mechanisms are behind it’, says Berezikov.
He has chosen these M. lignano worms because they regenerate quickly (have a high regeneration capacity) and are small and transparent. This makes them perfect for studying how regeneration works and how stem cells accomplish this feat.
The fact that they lay eggs all year round makes them ideal for genetic modification. ‘My lab is devising various genetic and genomic instruments and methods for developing the genome of this worm’, says Berezikov. ‘This can then be used as a regular model organism for stem cell research, possibly throughout the world.’
But Berezikov also has other reasons for choosing to work in an institute like ERIBA. He is keen to create an inspiring environment for future generations of scientific ‘leaders’. ‘I want to give talented postdoc researchers the time and space they need to conduct their research and develop into independent researchers.’
His theory works. He has built up a close team that enjoys working together, even if each researcher is concentrating on his/her own part of the project. ‘Building a team like this takes time’, explains Berezikov. ‘But nowadays, we even meet up on our days off.’
We all want to stave off the aches, pains and diseases of old age. In her research, biochemist Liesbeth Veenhoff is trying to find out exactly what happens to cells during the ageing process. ‘Ageing is all about the ageing of the body’s cells,’ explains Veenhoff. ‘Which molecules inside the cells multiply and which decline during this process?’
Cell definitively have tricks to stay young, she says. ‘We just need to find out what they are.’
She thinks that baking yeast will help her. In molecular terms, it is very similar to human cells, with the added advantage that baking yeast does not just give you the cells, but also the entire ‘creature’, the living organism to which they belong. ‘What’s more’, continues Veenhoff, ‘you can easily generate large numbers of cells.’
The good thing about a yeast cell is that during cell division, everything that causes ageing stays in the mother cell, while all the young material moves into the daughter cell. ‘This allows you to study, or perhaps I should say measure, how the daughter cell differs from the mother cell and to pinpoint the changes that cause ageing’, says Veenhoff. ‘It helps us to sort the important changes from the distractions.’
Ageing and rejuvenation processes
Veenhoff hopes that her research will show her precisely which molecular processes are involved in ageing and rejuvenation, and thinks that this is the first step. Her research may eventually lead to better drugs or targeted lifestyle changes.
Veenhoff’s team consists of five PhD students and postdoc researchers, all trying to find answers to questions about ageing. They work in the lab, growing yeast, performing difficult technical tasks and doing their bit for the project as a whole. ‘They are all free to decide how to carry out their own part of the research’, says Veenhoff.
She supervises her students for four years, until they finish their PhDs. ‘I love this aspect of my work’, she says. ‘You watch them develop, working hard and improving all the time. The absolute highlight is when one of them surprises me with a novel idea that had never even occurred to me.’