Transposable elements and the control of transcriptional networks
Human brain development differs markedly from that of other mammals and its developmental complexity is thought to be important for the emergence of higher cognitive functions. How this complexity and diversity is achieved remains largely unknown.
We have become interested in molecular mechanisms that control transposable elements (TEs) during brain development. Since TEs have entered the genome as mobile elements there are major difference in the genomic composition of TEs between species. As a result, TEs are potentially contributing to species-specific gene regulatory networks and it is tempting to speculate that TEs have contributed to the evolution of primates and humans, including the emergence of the complex primate brain.
We are currently focusing on understanding the role of the epigenetic co-repressor protein TRIM28 in the control of TEs in the human brain. We have recently shown that TRIM28 controls specific types of TEs and also nearby genes in mouse and human neural progenitor cells. Our current research therefore focuses on further understanding the role of TRIM28 in the control of TEs and how TEs control gene regulation in the developing and adult brain. These studies have the potential to implicate transposons in the control of gene regulation in human brain, hereby suggesting that they have played a key role in human evolution.
This project is supported by: Barncancerfonden, Hjärnfonden
Non-coding RNAs and neural stem cells
A long-standing interest of our lab is the functional analyses of miRNAs and their role in neural stem cells. We have during recent years, developed and optimized several tools that allow us to visualize and manipulate miRNA activity in vitro and in vivo. Our current research focuses on the characterization and identification of known and novel RNAs bound to the mouse and human RNA induced Silencing Complex in various cell types of the brain. We also perform translational studies on biopsies obtained from patients with brain tumors.
This project is supported by: Vetenskapsrådet, SSF, Cancerfonden
Autophagy and transcriptional control: implications for neurodegenerative disorders
Another focus in the lab is to understand how alterations in autophagy contribute to the pathophysiology of chronic neurodegenerative disorders of the CNS, such as Parkinson’s disease (PD) or Huntington’s disease (HD). We are using both animal models as well as reprogramming technologies to establish a variety of different patient derived neurons of disease relevant subtypes from patient fibroblasts. We are currently focusing on how alterations in autophagy result in impaired transcriptional control and perform epigenomic, transcriptomic and proteomic analyses to mechanistically understand these processes.
This project is supported by: Vetenskapsrådet, SSF, Tore Nilsons Research Grant, Greta och Johan Kocks Research Grant, Royal Physiographic Society of Lund Research Grant
Development of new gene therapy tools for the brain
We have during several years exploited and further developed AAV and lentiviral based vector systems as tools to genetically modify various types of neural cells including neural stem cells, astrocytes and neurons in vitro and in vivo. Currently our work is focused on the development of vector-based strategies of CRISPR/Cas9-mediated gene editing in the brain for experimental and therapeutic purposes.
This project is supported by: Vetenskapsrådet, Åhlen Research Grant, Åke Wibergs Research Grant, Royal Physiographic Society of Lund Research Grant, Anna-Lisa Rosenberg Research Grant