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Friedreich’s ataxia is a rare, inherited disease that causes progressive nervous system damage, impairing balance and coordination and leaving patients unable to walk by early adulthood. Now, researchers have found that treatment with continuous hypoxia — low-oxygen conditions comparable to levels at a Mount Everest base camp — restores balance and coordination in a mouse model of Friedreich’s ataxia. With further development, the findings could inform a potential treatment that lowers oxygen levels in certain tissues in humans to reverse advanced disease.
To mark the 10- and 20-year anniversaries of the Broad Summer Scholars Program and the Broad Summer Research Program respectively, we spoke with more than a dozen alumni about the impact these research experiences had on them. For many, doing research at the Broad as high school or college students changed their lives and put them on a path towards careers in STEM.
The Broad Summer Scholars Program and the Broad Summer Research Program aim both to teach students the research skills they need to succeed in the lab, and help them feel a sense of belonging there. Since the inception of the programs, more than 300 high school and college students have done research at the Broad. Many say that their experiences helped them identify a career path or part of science that interests them, learn how to think like a scientist, and feel more confident bringing their whole selves to the lab.
Researchers from the lab of Anna Greka, an institute member at the Broad, have developed a platform called FALCON (Fatty Acid Library for Comprehensive ONtologies) that can systematically profile the effects of a wide range of different free fatty acids in any cell type of interest, including cellular models of disease. The method allows scientists to expose cells to a large number of free fatty acids, mimicking conditions in the body, and to measure changes in the cells’ gene activity, shape or morphology, survival, and other key characteristics. They found that some monounsaturated fatty acids — long thought to be beneficial for health — are actually toxic to cells. They also identified genes that might explain how high fat levels in the blood can boost diabetes risk in those who are genetically susceptible to the disorder.
A new method from the lab of Xiao Wang is the first large-scale approach to track many mRNAs at once, over both space and time in individual cells. Maps generated by the method, known as TEMPOmap, can help uncover new principles of gene regulation and explore how RNA life cycle patterns influence the function of various cell types in health and disease. “Biology is, by nature, a dynamic process,” said co-first author Jingyi (Rena) Ren. “By following these RNAs, we can help answer some fascinating biological questions.”
Dysregulation of the complement system has been linked to Alzheimer’s disease and schizophrenia, and researchers have identified the first known regulator of the cascade in the adult brain: the neuronal pentraxin Nptx2. Loss of the protein led to complement overactivation and synapse loss, and boosting it reversed these effects, suggesting that therapies targeting the complement system could one day help treat neurodegenerative disease. “Findings like this help us learn what mediates the synapse loss and cognitive decline that is devastating for patients and their families,” said study co-senior author Borislav Dejanovic.
Researchers have harnessed a natural bacterial system to develop a new programmable protein delivery approach that works in human cells and animals. The system could potentially be a safe and efficient way to deliver gene therapies and cancer therapies. “Delivery of therapeutic molecules is a major bottleneck for medicine, and we will need a deep bench of options to get these powerful new therapies into the right cells in the body,” said Feng Zhang, the study’s senior author. “By learning from how nature transports proteins, we were able to develop a new platform that can help address this gap.”
In a #WhyIScience Q&A, clinical psychologist and postdoctoral fellow Susan Kuo talks about her work studying the relationships between genetic backgrounds and specific traits across development in autism and schizophrenia — and how she hopes to use clinical tools to support the wide-ranging ways in which people experience developmental differences and mental health challenges. “I believe that as we become more deeply aware of the diversity in people’s abilities and needs,” said Kuo, “we’ll be better equipped to build clinical tools that are more flexible, for more people, that support them more in the ways they want to be supported.”
Common DNA variants have yielded troves of info about complex disease genetics and risk, but gaining the same level of knowledge from rare coding mutations has proven challenging. Turning to UK Biobank and Genebass, Daniel Weiner, Ajay Nadig, Luke O'Connor, and colleagues have developed a method called BHR that allows researchers to gain new insights about rare variants' influence on heritability, and highlights the ways in which rare mutations can fuel insights about the core biology of common disease. https://broad.io/Rare-genetic-variants-news
A new method is revealing key cell structures and changes in gene expression near amyloid plaques and tau tangles in a mouse model of Alzheimer’s disease. Called STARmap PLUS, the technique is the first to simultaneously map gene expression of individual cells, their location, and the spatial distribution of specific proteins in intact tissue samples. The findings give scientists a clearer picture of how cells respond to the protein deposits in the brain — and could one day help evaluate existing Alzheimer’s treatments and develop new ones.
