The continuous replacement of neurons in the olfactory epithelium provides an advantageous model for investigating neuronal differentiation and maturation. By calculating the relative enrichment of every mRNA detected in samples of mature mouse olfactory sensory neurons (OSNs), immature OSNs, and the residual population of neighboring cell types, and then comparing these ratios against the known expression patterns of >300 genes, enrichment criteria that accurately predicted the OSN expression patterns of nearly all genes were determined. We identified 847 immature OSN-specific and 691 mature OSN-specific genes. The control of gene expression by chromatin modification and transcription factors, and neurite growth, protein transport, RNA processing, cholesterol biosynthesis, and apoptosis via death domain receptors, were overrepresented biological processes in immature OSNs. Ion transport (ion channels), presynaptic functions, and cilia-specific processes were overrepresented in mature OSNs. Processes overrepresented among the genes expressed by all OSNs were protein and ion transport, ER overload response, protein catabolism, and the electron transport chain. To more accurately represent gradations in mRNA abundance and identify all genes expressed in each cell type, classification methods were used to produce probabilities of expression in each cell type for every gene. These probabilities, which identified 9,300 genes expressed in OSNs, were 96% accurate at identifying genes expressed in OSNs and 86% accurate at discriminating genes specific to mature and immature OSNs. This OSN gene database not only predicts the genes responsible for the major biological processes active in OSNs, but also identifies thousands of never before studied genes that support OSN phenotypes.

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The continuous replacement of cells in the spiny lobster olfactory organ depends on proliferation of new cells at a specific site, the proximal proliferation zone (PPZ). Using representational difference analysis of cDNA, we identified transcripts enriched in the PPZ compared to the mature zone (MZ) of the organ. The 12 clones identified included four novel sequences, three exoskeletal proteins, a serine protease, two protease inhibitors, a putative growth factor, and a sequence named PET-15 that has similarity to antimicrobial proteins of the crustin type. PET-15 mRNA was only detected in epithelial cells. It was abundant in all epithelial cells of the PPZ, but was only detected in the MZ at sites of damage to the olfactory organ. PET-15 mRNA was increased by types of damage that are known to induce proliferation of new olfactory sensory neurons in the olfactory organ. It increased in the PPZ after partial ablation of the olfactory organ and in the MZ after shaving of aesthetasc sensilla. These ipsilateral effects were mirrored by smaller increases in the undamaged contralateral olfactory organ. These contralateral effects are most parsimoniously explained by the action of a diffusible signal. Because epithelial cells are the source of proliferating progenitors in the olfactory organ, the same diffusible signal may stimulate increases in both cellular proliferation and PET-15 mRNA. The uniformity of expression of PET-15 in the PPZ epithelium suggests that the epithelial cells that give rise to new olfactory sensory neurons are a subset of cells that express PET-15.

The overarching goalsof the University of Kentucky (UK) IMERS workshops, supported by an IPERT grant, are to empower faculty at minority‐serving institutions (MSIs) to develop and submit competitive research proposals through intensive grant‐writing skills training; to build research‐related individual and institutional capacity through training on mentorship of student researchers; and to sustain workshop momentum by embedding multiple levels of mentored proposal development support during and after each workshop. We hypothesize that this targeted training will enhance the research environment at MSI's, increase the diversity of NIH‐funded investigators and improve the training of underrepresented students in biomedical research, thus providing a feed‐forward mechanism to expand the diversity of the US biomedical workforce in future years. A hallmark of IMERS is to engage participants in hands‐on, active‐learning style grant‐writing training for faculty who are poised to submit NIH proposals ranging from development/exploratory to R01s. This training is provided by UK faculty and experienced research development professionals. The IMERS model incorporates guided writing, participatory training, and active learning. Training is comprised of several modalities. First, IMERS offers two 3‐day grant‐writing retreats/year on the UK campus. These workshops are designed for highly motivated investigators who have submitted proposals to NIH without success and those who have been actively planning NIH submission; ~25 faculty are selected for each workshop via an on‐line application. On‐site workshops include consultation with actively funded UK investigators and staff from the UK Proposal Development Office; we strive to maintain post‐workshop interactions between participants and UK faculty/staff. Three 2‐day off‐site workshops/year are also offered. The IMERS staff will work with off‐site institutions to tailor the workshops to specific needs. In‐person workshops have been postponed due to COVID‐19 restrictions, but will resume when safe to do so. However, we have developed an active series of virtual workshops and seminars during this time, and we anticipate that these and additional on‐line activities will continue as a third arm of training even after restriction are lifted. Travel and lodging expenses for faculty to attend UK workshops, for the IMERS team to travel, are covered by the grant. Workshop sessions cover numerous topics, including: using NIH resources for program/funding information, budget issues, the proposal review process, writing a high‐impact specific aims page and an effective research strategy, rigor and reproducibility, responsible conduct of research, NIH Biosketch, navigating the NIH resubmission process, and mentoring student researchers. Program evaluation, based in part on participant survey data, communication email and an active ListServ and subsequent submission rate and success, validates that program participants have increased confidence in their grant‐writing abilities and are succee...