networking
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Structure-function and mechanistic studies of a specific glycosyltransferase complex in fusion-driven pediatric gliomas
Abstract Glycosylation is a co/post-translational modification involved in cell-matrix interactions, antigen-antibody interactions, tumor invasion, and cell motility. Abnormal glycosylation is a hallmark of cancer, with various glycosylation-related genes linked to glioma prognosis and tumor heterogeneity. Pediatric low-grade gliomas (pLGGs) stand as the most common childhood central nervous system tumor, accounting for 30%-40% of all CNS tumors in children. Despite its relatively low mortality rate, pLGGs are associated with devastating lifelong morbidity. The most common alteration found in 75% of tumors is the KIAA1549:BRAF fusion, causing an aberrant activation of the MAPK/ERK signaling pathway. Current treatments, such as traditional chemotherapies and targeted therapies, have limitations such as resistance, lack of specificity, toxicity and paradoxical activation of the MAPK pathway. This highlights the urgent need for novel therapeutic approaches. Investigations into KIAA1549:BRAF-driven pLGGs identified their dependency on the protein-O-mannosyl transferase (POMT) complex for survival. In contrast, BRAFV600E-mutant cells did not show dependency, suggesting the POMT complex as a vulnerability and promising target in KIAA1549:BRAF-driven pLGGs. Therefore, our goal is to characterize the POMT complex structurally and biochemically and study its roles in KIAA1549:BRAF-driven pLGGs. In this proposal, we aim to 1) determine the high-resolution structures of the complex in its unbound, substrate-bound, and inhibitor-bound forms and 2) elucidate the POMT complex mechanisms in KIAA1549:BRAF-driven pLGGs. We will define the critical functional domains, active sites, interaction interfaces and translational modifications crucial for enzymatic activity using cryo-EM techniques, mutagenesis, and functional studies. To study biological pathways and molecular events modulated by the POMT complex, we will implement global proteomics and transcriptomics analysis in well-characterized disease models. In parallel, we will assess the effect of the POMT complex on the MAPK/ERK signaling pathway. This study will guide the structure-based design of probes and drugs targeting the POMT complex and will unveil glycosylation-mediated oncogenesis in pediatric gliomas. It will aid in the development of new targeted therapies and the identification of new biomarkers for pLGGs harboring the KIAA1549:BRAF fusion. The research will be conducted in the Fischer lab at Dana-Farber Cancer Institute, which provides a collaborative and resource-rich environment. The career development plan includes training in scientific writing, mentoring, and presentation skills, as well as interdisciplinary networking with experts in structural biology and pediatric oncology. The candidate’s career goal is to establish an independent research laboratory focused on developing new therapeutic modalities for pediatric neurooncology. The training provided through this fellowship represents a critical step toward achieving this goal.
ALBA mentoring fireside chats: identifying mentorship needs
This is the first session in a series of three online fireside chats organised by the ALBA Network with the aims of understanding what’s not working in existing mentoring programmes in (neuro)science and identify the challenges and unmet mentorship needs of the next generation of scientists across the globe. The feedback from these sessions will be used to develop a tailored ALBA mentoring programme.
A Toolkit to Succeed in Neuroscience in Africa - an IBRO-ALBA-WWN-SANS Webinar
Following up on last year's webinar - What it takes to succeed as a neuroscientist in Africa, this panel discussion aims at creating a guide to the skill set needed to be a neuroscientist in the African continent. Chairs and panelists will illustrate different areas of expertise as part of the "Toolkit" by matching them to real life experience and solutions that they had to find while building their career as scientists.
ALBA-WWN Webinar: What it takes to succeed as a neuroscientist in Africa
In this webinar, the ALBA Network & World Women in Neuroscience partner to address equity, inclusion & diversity issues across the Sub-Saharan African neuroscience community. The panel discussion will explore the challenges and biases faced by African neuroscientists while establishing their careers - focusing on a lack of mentoring and networking but also on the difficulties to raise funding - as well as display the strengths present in the region, which can be exploited to find solutions. Registration is free but required: https://www.alba.network/alba-wwn-webinar-africa
Networking—the key to success… especially in the brain
In our everyday lives, we form connections and build up social networks that allow us to function successfully as individuals and as a society. Our social networks tend to include well-connected individuals who link us to other groups of people that we might otherwise have limited access to. In addition, we are more likely to befriend individuals who a) live nearby and b) have mutual friends. Interestingly, neurons tend to do the same…until development is perturbed. Just like social networks, neuronal networks require highly connected hubs to elicit efficient communication at minimal cost (you can’t befriend everybody you meet, nor can every neuron wire with every other!). This talk will cover some of Alex’s work showing that microscopic (cellular scale) brain networks inferred from spontaneous activity show similar complex topology to that previously described in macroscopic human brain scans. The talk will also discuss what happens when neurodevelopment is disrupted in the case of a monogenic disorder called Rett Syndrome. This will include simulations of neuronal activity and the effects of manipulation of model parameters as well as what happens when we manipulate real developing networks using optogenetics. If functional development can be restored in atypical networks, this may have implications for treatment of neurodevelopmental disorders like Rett Syndrome.
ALBA-BIN Networking event: Black in (N)Euro
The ALBA Network and Black in Neuro are partnering to bring the Black neuroscientific community in Europe together. Are you a Black neuroscientist based in Europe? If so, join us for this casual online networking event. We will share our experience, stories and knowledge about what it is to be black in Europe while working in brain research. We will also discuss potential actions ALBA and BiN could take to provide better visibility to the community. This is a time to get to know each other, share, network and relate. Please register to receive the link to the zoom meeting.
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