What if you are reading something out loud, while listening to your own delayed voice? How does this affect your reading skills?
Virtual reality glasses
Can you stay in balance if you do not know what is real and what not?
Are you balanced enough to escape this maze?
HAL Allergy is a modern company with high quality pharmaceutical GMP manufacturing and research facilities located in the Leiden Bio Science Park. With offices in seven European countries, we are one of the top European players in the field of allergy diagnostic and treatment.
Synergistic effects of stress, the neuroimmune system and nutrition in early-life stress
induced cognitive decline
Kitty Reemst, Kit-yi Yam, Lianne Hoeijmakers, Eva F.G. Naninck, Eline, M. van der Beek,
Lidewij Schipper, Annemarie Oosting, Paul, J. Lucassen, Aniko Korosi
Early-life stress effects the brain for life. Clinical and pre-clinical evidence shows that early-
life stress (ES), malnutrition and infection can all lead to cognitive impairments and
increased vulnerability to develop psychopathologies later in life. We investigate the
synergistic effects of stress, nutrition and the neuroimmune system early in life. Given the
high nutritional demand of the brain during development, early nutrition is critical for brain
programming. Long-chain polyunsaturated fatty acids (LCPUFA’s) have immunomodulatory
roles and the ratio between omega-6 and omega-3 fatty acids is critical for brain development
and function. We propose that an early dietary intervention with an improved lipid content
might be protective against ES-induced functional deficits, and that the neuroimmune system
is involved in mediating these effects. We have previously shown that chronic ES exposure
induces cognitive decline in mice, which correlates with a reduction in hippocampal
neurogenesis in adulthood. Also, ES also affects the neuroimmune cells of the brain, as ES-
exposed mice display more IBA1 and CD68 expressing hippocampal microglia compared to
We investigated if a dietary intervention with essential LCPUFA’s can modulate ES-
induced effects and which are the neurobiological substrates for the beneficial effects of the
diet. We found that early dietary intervention (P2 – P42) with a reduced n-6/n- 3 ratio is able
to prevent ES-induced cognitive decline. This rescue was accompanied by restoration of ES-
induced reductions in hippocampal newborn cell survival and increased hippocampal CD68
expression, suggesting that the beneficial effect of the diet is mediated by modulating
hippocampal neurogenesis and microglia functioning. The exact role of altered microglia
activity in this context is currently under investigation.
Concluding, ES-induced cognitive decline can be prevented by nutritional
intervention with improved lipid content, and affects neurogenesis and the neuroimmune
system. This gives new insights for the development of targeted dietary interventions for
Combining genome editing with quantitative microscopy: measuring the dynamics of the WNT/beta-catenin pathway
Saskia de Man, Anoeska van de Moosdijk, Lotte Hofstee, Jasmijn Span, Mark Hink, Renée van
Wnt/beta-catenin signalling is key to normal development and homeostasis, as it controls the
balance between cell division and differentiation. Accordingly, hyperactivation of the pathway is
often found in cancer. Mutation of beta-catenin (CTNNB1) is observed in many different cancers.
Although these mutations contribute to activation of the pathway, a detailed understanding of how
different mutations affect CTNNB1 protein dynamics and signalling output remains elusive.
We have used CRISPR/Cas9 to endogenously tag CTNNB1 with fluorescent proteins in several cell
lines. We are able to image CTNNB1 fusions and quantify concentrations and diffusion
characteristics of the tagged beta-catenin in living cells with fluctuation correlation spectroscopy
(FCS). Currently we are working to create oncogenic variants of beta-catenin to more fully
understand their behaviour, as well as other mutant forms of CTNNB1 to determine the role of
different domains in localization, interaction partner binding and signal transduction.
Tracing stem cells in multicolour
Anoeska van de Moosdijk, Britt van der Swaan and Renée van Amerongen
Adult stem cells exhibit a remarkable potential to develop into many different cell
types and have been identified in most mammalian tissues. With their great capacity
to self-renew, stem cells are crucial for tissue development and long-term
maintenance of tissue homeostasis, processes mediated through Wnt-signalling. To
investigate how adult stem cells contribute to a dynamic tissue such as the mouse
mammary gland, lineage tracing analysis has been widely used, revealing cell fate
and proliferation in vivo. This technique allows us to permanently label cells, so their
offspring will also carry that label. An inducible driver line provides spatio-temporal
control over the labelling. One such a driver line uses the Wnt target gene and known
stem cell marker Axin2. Although the currently available mouse models provide us
with knowledge on Wnt-responsive stem cells in the mammary gland during
development and pregnancy (van Amerongen et al., 2012), they have some
important drawbacks. Therefore, we are building the next generation of genetically
engineered mouse models.
Clocks in the brain
Circadian rhythms (day and night rhythms) are present everywhere in nature: bacteria, yeasts, plants
and animals all keep track of time. What’s more, organs function in a daily rhythm, virtually all cells
in the body have clocks and the expression of many genes is rhythmic. A little nucleus in the brain,
the SCN, makes sure that all these ticking clocks keep the rhythm but shift work or a jet lag can
disrupt this. New insights in circadian rhythms are rapidly emerging and reveal the underlying
mechanisms, their function and what happens when these rhythms get disrupted. However, there
are still many questions to be answered. Many stem cells, for instance, show circadian rhythms,
What about adult neural stem cells? How does it work and is it important for learning and memory?