WashU-Warwick Research Collaborations
WashU Global Incubator Seed Grant awardees
Leveraging Actin Methylation by SETD2 to Treat Clear Cell Renal Carcinoma (2005 )
WashU PI: Silvia JansenLink opens in a new window, Cell Biology & Physiology, WashU Medicine
University of Warwick collaborator: Mohan Balasubramanian, Warwick Medical School
Development of chemoresistance is a rising problem and is emerging as the leading cause of tumor metastasis and patient relapse. As such, there is an increasing need to develop anti-cancer strategies that are directed against different cellular systems than the ones that are currently targeted. Because of its critical roles in cell migration, differentiation, and proliferation, the actin cytoskeleton is strongly linked to cancer progression and thus makes an attractive alternative target. However, this has proven difficult, as all available anti-actin agents have major side effects. We propose here to determine the potential of actin posttranslational modifications to treat cancer. Specifically, we will investigate how actin methylation contributes to SETD2 tumor-suppression in clear cell renal carcinoma using a combination of engineered carcinoma lines and in vitro analysis of methylated actin. Collectively, the proposed experiments will lay the foundation for future studies focused on developing actin posttranslational modifications into novel anti-tumor strategies.
Local protein synthesis and the assembly of the centrosome-cilium complex (2004)
WashU PI: Jennifer Wang, Biology, Arts & Sciences
University of Warwick collaborator: Erik Griffin, School of Life Sciences
The centrosome-cilium complex is a conserved animal organelle that underlies the organization of cells and their ability to signal to each other. Defects in centrosomes and cilia are linked to human diseases including cancer, microcephaly, dwarfism, and ciliopathies, highlighting the importance of understanding how these organelles form. Through a poorly understood process, they are built from hundreds of proteins that must find each other and coalesce with in a cell’s cytoplasm. To understand where these proteins come from within the cell as they seek each other out, we will image when and where centrosome-cilium proteins are made within living cells, using both the nematode C. elegans and human tissue culture cells as experimental systems. We will integrate expertise in genetics (Dr. Griffin; Warwick) and centrosome-cilium biology (Dr. Wang; WashU) to understand how these critical organelles assemble.
Thermal stress memory for sustainable agriculture (2004)
WashU PI: Xuehua Zhong Biology, Arts & Sciences
University of Warwick collaborator: Jose Gutierrez-Marcos, School of Life Sciences
Plants are significant sources of food, feed, fiber, fuel, and medicine. Climate change together with other environmental assaults represent constant threat for plant survival and productivity. Thus, there is an urgent need to develop “climate resilient plants” to cope with varying environmental conditions for sustainable agriculture. This project aims to address these challenges by understanding how plants cope with environmental stresses and how do they reprogram the chromatin and transcriptional landscapes to generate adaptive responses. Specifically, we investigate dynamic epigenome alterations in response to heat stress, heat-induced epigenetic memory, and transgenerational epigenetic inheritance. As we probe basic principles governing epigenetic regulation that are conserved across eukaryotes, the findings gained from this pioneering project will be readily applicable to a wide range of plant species. Such knowledge will lead to the development of novel strategies that harness epigenetic regulation to develop sustainable, nutritious, and resilient crops, thereby revolutionizing the agricultural landscape