Catch up on some of the recently awarded grants, including a new multi-omics consortium to improve understanding of a variety of diseases, studying molecular aspects of Alzheimer’s pathology and developing a new microscope to image cellular mechanics in vivo.
The news highlights:
- The Beckman Institute will collaborate with Minecraft to develop a 4D interactive model of living cells
- NIH awards $50.3 million to new multi-omics consortium
- Dissecting the molecular basis of quality control pathways
- $2.6 million awarded to study molecular aspects of Alzheimer’s pathology
- A new Brillouin microscope for in vivo imaging of cellular mechanics
The Beckman Institute will collaborate with Minecraft to develop a 4D interactive model of living cells
The National Science Foundation (NSF; VA, USA) is providing $30 million to the NSF Science and Technology Center for Quantitative Cell Biology to create whole-cell models including both spatial and temporal factors. The center will partner with the open-world video game Minecraft to create an interactive full living cell and an immersive learning experience. With this new model, they hope to advance the study of healthy and diseased cells and accelerate research into gene expression, metabolism and division, and use the tool for educational purposes.
“Now is the right time to start such a moon-shot effort,” commented Zan Luthy-Schulten (University of Illinois Urbana-Champaign, IL, USA), the principal investigator of this study. “The computational and experimental capabilities are just at the verge of where this effort is realistic to contemplate, and this is usually when breakthroughs happen. Whole-cell models are now at the transition point between what is possible already and what is not yet possible.”
The model will consist of a full quantitative description of both the physical and chemical processes that define a cell state, including a cell’s shape, size and microscopic ultrastructure; its composition of elements such as metabolites, organelles, proteins, lipids and nucleic acids; its full network of inner reactions and signaling; and its interactions with the outside environment.
To accomplish this, the researchers will use a variety of imaging and simulation tools including cryo-electron microscopy and tomography, label-free microscopy and MINIFLUX, a super-resolution microscopy technique that accurately locates and tracks biomolecules in live cells.
NIH awards $50.3 million to new multi-omics consortium
The National Institutes of Health (NIH; MD, USA) is establishing the Multi-Omics for Health and Disease Consortium, awarding $50.3 million over 5 years – pending the availability of funds – which is jointly funded by the National Institute of Environmental Health Sciences, the National Cancer Institute and the National Human Genome Research Institute (NHGRI). Approximately $11 million will be awarded in the first year.
Around half of the funds will support studies in fatty liver diseases, hepatocellular carcinoma, asthma, chronic kidney disease and preeclampsia, among others. Additionally, at least 75% of participants will be from ancestral backgrounds that have been underrepresented in genomics research. The researchers will analyze genomic, epigenomic, transcriptomic, proteomic and metabolomic data obtained from each participant’s biological sample to generate molecular profiles of disease and non-disease states. The resulting datasets will be made available to the wider scientific community for further studies.
“Beyond gaining insights into individual diseases, the primary goal of this consortium is to develop scalable and generalizable multi-omics research strategies as well as methods to analyze these large and complex datasets,” explained Joannella Morales (NHGRI), a program director involved in leading the consortium.
The consortium will also consider and collect data on participants’ environmental and social determinants of health and combine this with multi-omics data for a more comprehensive view of factors that contribute to disease risk and outcomes.
“Multi-omics studies are at the forefront of biomedical research and promise to advance our understanding of disease onset and progression,” commented Erin Ramos (NHGRI). “All while potentially providing important clues for treatment design and drug-discovery efforts. This new consortium is an important step in making those advances a reality.”
Dissecting the molecular basis of quality control pathways
Zhihao Wu, a professor at South Methodist University (TX, USA), has been awarded $1.8 million over 5 years from the Maximizing Investigators’ Research Award (MIRA) from the NIH to determine if different, seemingly unrelated quality control pathways in our bodies might be collaborating to repair damaged components in cells. This could explain why breakdowns in different quality control pathways lead to the same abnormal changes observed in several diseases including Parkinson’s and Alzheimer’s, Type II diabetes and cancer. This could lead to new therapeutic targets.
“Intriguingly, pathological hallmarks caused by quality control defects – such as defective protein accumulation and essential organelles (mitochondria) losing their function – often co-occur in many human diseases, suggesting that different quality control pathways may interact and assemble a network in response to diverse types of cellular stress,” explained Wu.
Following Wu’s previous work, his team will look at dissecting the molecular basis of three known pathways: ribosome-associated translation quality control, macromolecule quality control and organelle quality control.
$2.6 million awarded to study molecular aspects of Alzheimer’s pathology
The NIH has awarded $2.6 million to Timothy Huang (Sanford Burnham Prebys, CA, USA) to study the link between a genetic variant of TREM2, a protein found in the brain’s immune cells, and Alzheimer’s disease.
A rare genetic mutation in TREM2 is associated with an increased risk of Alzheimer’s in some individuals, despite it potentially reducing levels of beta-amyloid. With this funding, Huang and his team will investigate this observation further and explore if the genetic variant has detrimental effects on tau – a protein that usually helps to stabilize neurons but when abnormal, forms ‘tau tangles’, which are characteristic of Alzheimer’s.
“Results from this study will allow us to better understand how an Alzheimer’s disease risk factor can reduce beta-amyloid levels, which are thought to be protective, yet increase the risk of disease onset,” explained Huang. “Since new treatments are focused on reducing amyloid levels, understanding how TREM2 genetic variants can reduce beta-amyloid yet confer increased risk of disease may give us further insight into improved or complementary drug treatments in the future.”
A new Brillouin Microscope for in vivo imaging of cellular mechanics
The European Innovation Council has awarded more than €3 million to the development of a new microscope for in vivo imaging of mechanical properties in cells – rigidity, stiffness and viscosity – called Micro4PAP (in vivo Brillouin Microscope with application to Protein Aggregation-based Pathologies). The project is led by the Italian Institute of Technology (Genoa, Italy).
The aim of this research project is to develop a fast-scanning Brillouin Microscope that can probe the mechanical properties of subcellular elements with 3D resolution and will be suitable for taking in vivo measurements of living cells. Micro4PAP could be applied to study pathologies of neurodegenerative disorders, tumors, chronic and age-related diseases, and be used in disease detection, diagnosis and therapy.
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