The grant of 850 000 euro will allow her to expand her research team to further investigate how changes in neuronal activity differentially affects AIS composition in excitatory and inhibitory neurons, and how this differential plasticity participates in network homeostasis during sensory-dependent experience.

This project will use proteomics and transcriptomics approaches in cultured neurons and in vivo, coupled to super-resolution imaging and electrophysiology.

There will be PhD and post-doc positions opening in the AIS lab (see lab website: https://cncr.nl/research-team/axon_initial_segment_biology/)

More information on awarded Vidi projects can be found here.

The awarded project, titled “Should I stay or should I go? Elucidating neuropeptidergic modulation of approach-avoidance behaviour” focuses on the neurobiological mechanisms that control our responses to challenging environments. In particular, Danai’s team will work on identifying how neuromodulators, such as norepinephrine and various neuropeptides, mediate behavioural choices during negative (stressful or threatening) experiences.

Taking advantage of a multilevel approach, that includes synaptic proteomics, electrophysiology and circuit manipulation in the behaving animal, Danai aims to highlight the endogenous systems that promote adaptive stress responses and prevent maladaptations linked to the development of psychopathology, inlcuding anxiety, impulse control and attentional disorders.

See the research team page for more information.

Kim (now a post-doc on a collaborative project of the labs of Max Koppers and Wiep Scheper) will share her research findings at the annual Alzheimer Nederland donor meeting and received 2500 euro to spend on her further personal development.

News item at Alzheimer Nederland:
https://www.alzheimer-nederland.nl/nieuws/kim-wolzak-wint-proefschriftprijs-alzheimer-nederland-2024

The grant of 1.5M euro will allow him to expand his research group to further investigate how specific mRNAs are captured at specific subcellular locations in neurons.

Brain function requires precise regulation of the neuronal proteome, which involves localizing thousands of mRNAs to neurites for their translation at specific subcellular locations. The mechanisms that ensure the correct localization, capture and translation of mRNAs remain elusive. A better understanding is urgent since dysregulation of mRNA localization is increasingly emerging as a pathological event in neurological diseases such as amyotrophic lateral sclerosis (ALS).

In this project, his group will use new genetic and imaging tools developed in the lab together with super-resolution microscopy, live-cell imaging and RNA sequencing to investigate how different organelles coordinate mRNA transport, localization and translation in neurons to support neuron function and survival. This will provide important new insights into the role of mRNA localization in neuron physiology and neurodegenerative diseases such as ALS.

The team’s website can be found here.

 

The teams consisted of researchers and clinicians from the Functional Genomics department of Vrije Universiteit Amsterdam, Human Genetics department of Amsterdam UMC, Amsterdam Neuroscience, Radboud UMC, University of Antwerp, and Antwerp University Hospital, as well as family members of STXBP1 patients. Each team biked more than eighty kilometers to the mid-point in Dordrecht, halfway between the labs of Amsterdam and the labs of Antwerp. In Dordrecht, all bikers were welcomed by supporters, family members of patients and colleagues.

We would like to thank all cyclists for their great achievement, the supporters for their enthusiasm and the sponsors for their donations. Especially Amsterdam Neuroscience for their generous donation of € 2.000,00! It has been heartwarming to see the overwhelming support for our cause. In total we raised € 6.359,00 and Penn State University will double this amount.

All donations have been transferred to the Million Dollar bike ride organization in the United States (team STXBP1). The Penn Medicine Orphan Disease Center will distribute the funds to the international scientific community through grant proposal applications. They will monitor and manage progress of the science and spending of the funds.

See the MDBR website for more information.

PSP and FTDs are part of a class of debilitating neurodegenerative diseases that may shorten a person’s lifespan, and for which no current treatments exist. The research program by van der Kant, is one out of four groundbreaking research projects funded through the Tauopathy Challenge Workshop, that will serve as building blocks toward ongoing efforts to find treatments and a cure for these diseases, known as primary tauopathies.

Work in the van der Kant lab focuses on examining how cholesterol, or other lipids, contribute to the tau pathology in PSP and FTD, knowing that recent studies have shown that excess levels of cholesterol in the brain can drive the build-up of tau. Dr. van der Kant will map how lipid metabolism in different iPSC-derived brain cell types is altered in these diseases, and how this might contribute to neuroinflammation. The project will help provide a better understanding of the early processes that drive PSP and FTDs.

Funding is awarded through the 2024 Tauopathy challenge workshop, which was held to close gaps in understanding and address current research challenges in primary tauopathies, such as Frontotemporal Dementias and Progressive Supranuclear Palsy. Funding was made available through the Rainwater Charitable Foundation in collaboration with the Aging Mind Foundation and the CurePSP foundation.

More information can be found here: https://rainwatercharitablefoundation.org/the-rainwater-charitable-foundation-curepsp-and-aging-mind-foundation-announce-2-million-in-grants-to-fund-innovative-research-projects-from-the-tauopathy-challenge-workshop/

Dr. Scheper, trained as an RNA biologist at Utrecht University, started working on the export of misfolded proteins from the endoplasmic reticulum during her time at Cambridge University, UK, and developed a strong research program in Amsterdam that investigates the role of proteostasis in neurodegenerative disorders such as Alzheimer’s disease, frontotemporal dementia and Parkinson’s disease. Since 2013, Dr. Scheper is principal investigator at FGA, and has built a multidisciplinary team and a prominent international reputation in the field, with excellent publications and strong external funding.  Dr. Scheper is also a familiar face in national media for outreach activities, laymen talks and fundraisers.

The purpose of the new chair is to initiate and conduct research to gain and deepen understanding of the role of proteostatic stress mechanisms in the pathogenesis of neurodegenerative diseases. This insight will lead to the identification of new targets for therapeutic intervention and associated biomarkers for therapy monitoring. Additionally, the chair focuses on the utilization of the results of this research through valorization towards the industry as well as science communication towards the general public.

Learn more about her research at her CNCR research page: https://cncr.nl/research-team/molecular_neurodegeneration_/ 

 

Dorret Boomsma received her two Master degrees in 1983 cum laude – one from the VU University in Amsterdam, in Psychophysiology and one from the University of Colorado, US in Behavior Genetics. After receiving her PhD cum laude from the VU in 1992 on the quantitative genetics of cardiovascular disease, she was appointed as an assistant professor at the VU University in Amsterdam, where she became the head of the Department of Biological Psychology in 1994.

Together with Prof Ko Orlebeke, Dorret Boomsma founded the Netherlands Twin Registry (NTR) in 1986, which currently consists of over 75,000 twins and their family members. The NTR has been and still is a tremendous success and an invaluable resource for the study of genetic and environmental influences on human nature, not only serving Dutch scientists, but facilitating worldwide collaborations. In thousands of scientific publications this resource has now been used, and Dorret’s work has delivered significant contributions to a broad spectrum of human behavior and disease, going from charting the relative influence of genes and environment to pinpointing the most likely causal genes using genomewide association tools and biomedical samples.

Dorret’s work has been lauded both nationally and internationally. She received numerous awards and prizes, including an advanced grant from the European Research Council (2008), the Ming Tsuang Life Time achievement award from the International Society of Psychiatric Genetics (2022), and an Honorary doctorate from the University of Helsinki Medical School (2022), Finland. In 2001 Dorret Boomsma received the Dutch Spinozapremie, which is said to be the Dutch equivalence of the Nobel Prize, recognizing her position as a top scientist.

The Department of Complex Trait Genetics is honored to be joined by Dorret Boomsma, she brings in a lifetime of scientific knowledge on quantitative and behavior genetics, an invaluable network of collaborations and worldwide recognition and opportunities, along with a spirit of unbridled scientific curiosity. The combination with the large scale genetic analyses conducted at CTG and the broader embedding in neuroscience and biology at the CNCR bears exciting future promises.

 

The high-resolution multi-omic atlas of chromatin accessibility and gene expression during the first-trimester of the developing human brain includes more than 100,000 cell-type- and region-specific developmental accessible chromatin regions, as well as inferred candidate cis-regulatory elements and their predicted regulatory effects. The resource allows for example linking transcription factors to putative enhancers, and enhancers to their target genes. In addition, this resource enables the interpretation of genetic associations with disease.

Marijn Schipper, PhD student at CNCR-CTG, investigated whether the parts of DNA that contain open chromatin in specific types of cells during early embryonic development overlap with genetic variants that have been identified previously in genomewide association studies for psychiatric disorders. We found that the patterns of open chromatin in the DNA in specific types of cells during development coincide with stretches of DNA that are also linked to ADHD, anorexia, autism spectrum disorders, depression, insomnia and schizophrenia. The strongest association was found for depression: genetic variants that have previously been linked to depression occur particularly frequently in stretches of DNA that are mainly active during early embryonic development in the GABAergic neurons in the midbrain. This link with the midbrain is novel, and offers new research directions with a specific focus on the midbrain for understanding the hereditary component of depression.

The paper can be found here: https://www.nature.com/articles/s41586-024-07234-1

News article VU website.

 

This study explains at the molecular level why synapses are stronger and depress faster in the absence of tomosyns. The research was mainly performed by Marieke Meijer (Amsterdam UMC), Miriam Öttl (Vrije Universiteit) and Jie Yang (Yale School of Medicine), among others, who combined synapse physiology on a conditional mouse model of tomosyn deficiency with single-molecule force measurements by the Yongli Zhang lab. Our data reveal that tomosyns produce a new intermediate state in SNARE assembly which drastically reduces the probability that synaptic vesicles fuse.

These findings offer a new explanation for the functional heterogeneity of synaptic vesicles (‘primed’ vs ‘superprimed’). By limiting the amount of synaptic vesicles that reside in a highly fusogenic state, tomosyns equalize neurotransmission during activity. This study also advances our understanding on how synapse function can be regulated by targeting the molecular machinery that releases neurotransmitters.

The paper can be found here: https://rdcu.be/dCvS8

Image credit: ‘fragment of vesicles’ by Rini Brakkee