Randomized Controlled Study to Test the Effectiveness of Developmental Network Coaching in the Career Advancement of Diverse Early-Stage Investigators (ESIs): Implementation Challenges and Lessons Learned

Introduction: Adding developmental networks (DN) to grant-writing coaching can significantly enhance ESIs’ research careers. Herein, we present study design, ESIs’ characteristics and encountered challenges/lessons learned and their resolutions when deploying/implementing (a) NCR algorithm(s), (b) recruitment/retention and (c) implementing DN intervention. Methods: Nested Cluster Randomization (NCR) design governs this study implementation. The sample size is 220 ESIs intending to submit an NIH K, R, U, and/or Minority Supplement application(s). Primary outcome: intensity/sustainability of grant submission(s)/funding(s), measured by time to/between application(s). Outcome(s) analyses modes: summaries, Kaplan Meir and Cox proportional hazard models as a function of randomization groups and other predictors of outcomes. Results: In the present study, we recruited two cohorts of ESIs (N = 85): 39% African Americans, 18% Latinx, 18% Whites, 20% Asians and 6% Hawaiian/Pacific Islander/other ethnicities; 65% are women; 73% are assistant professors, 4% are Associate Professors and 23% are instructors/scientists/post-doctoral. Participants’ disciplines: 32% basic/biomedical, 36% clinical/translational and 32% social/behavioral. Proposal(s) mechanisms: 61% research grants (R series), 31% career development (K series), 7% support of competitive research (SCORE) and 1% National Science Foundation applications. NCR did produce balance in the distribution of ESIs’ demographics, sex at birth, ethnicity, professional appointments, background disciplines, and mechanism of sought funding. Lessons learned/challenges: NCR implementation was methodologically challenged during implementation by added constraints (e.g., assigning coaches to the same randomization arm of their participants as well as blinding them to ESIs’ randomization group). Recruitment and retention were hampered by the COVID-19 pandemic and more progressive and innovative strategies were needed to heighten the visibility and outreach of this program. DN delivery was also affected by the pandemic and monitoring of ESIs’ engagement and facilitation of communications interventions were needed. Resolution of these challenges effectively reconfigured NCR algorithms, recruitment/retention plans, and DN intervention delivery. We intend to recruit an additional 135 ESIs focusing on underrepresented scholars from RCMIs, CTSAs, and other programs. COVID-19 rendered this program 100% virtual, with recruitment/retention challenges and substantial disruption of ESIs’ research. We may extend the grant writing period, coaching, and Mock Study Section support.

H2O2 Induces Major Phosphorylation Changes in Critical Regulators of Signal Transduction, Gene Expression, Metabolism and Developmental Networks in Aspergillus nidulans

Reactive oxygen species (ROS) regulate several aspects of cell physiology in filamentous fungi including the antioxidant response and development. However, little is known about the signaling pathways involved in these processes. Here, we report Aspergillus nidulans global phosphoproteome during mycelial growth and show that under these conditions, H2O2 induces major changes in protein phosphorylation. Among the 1964 phosphoproteins we identified, H2O2 induced the phosphorylation of 131 proteins at one or more sites as well as the dephosphorylation of a larger set of proteins. A detailed analysis of these phosphoproteins shows that H2O2 affected the phosphorylation of critical regulatory nodes of phosphoinositide, MAPK, and TOR signaling as well as the phosphorylation of multiple proteins involved in the regulation of gene expression, primary and secondary metabolism, and development. Our results provide a novel and extensive protein phosphorylation landscape in A. nidulans, indicating that H2O2 induces a shift in general metabolism from anabolic to catabolic, and the activation of multiple stress survival pathways. Our results expand the significance of H2O2 in eukaryotic cell signaling.

Construction of Anatomical Structure Specific Developmental Dynamical Networks for Human Brain on multiple Omics Levels

Background: Human brain development is a series of complex processes exhibiting profound changes from gestation to adulthood. Objective: We aimed to construct dynamic developmental networks for each anatomical structure of human brain based on omics’ levels in order to gain a new systematical brain map on molecular level. Method: We performed the brain development analyses by constructing dynamical networks between adjacent time points on different grouping levels of anatomical structures. The gene-time networks were first built to get the developing brain dynamical maps on transcriptome level. Then miRNA-mRNA networks and protein-protein networks were constructed by integrating the information from miRNomics and proteomics. The time and structure-specific biomarkers were filtered based on analyses of topological characters. Results: The most dramatical developmental time and structure were fetal-infancy and telencephalon, respectively. Cortex was the key developmental region in ‘late fetal and neonatal’ and ‘early infancy’. The development of temporal lobe was different from other lobes since the significant changes of molecules were found only in the comparison pair ‘early fetal-early mid-fetal’ and ‘adolescence-young adulthood’. Interestingly, the changes among different brain structures inside adolescence and adulthood were bigger than other time points. hsa-miR-548c-3p and H3C2 may be new brain developments indicators considering their key roles in networks. Conclusion: To our knowledge, this study is the first report of dynamical brain development maps for different anatomical structures on multiple omics’. The results provide a new sight of brain development in a systematical way which may provide a more accurate understanding of human brain.