# Investigating the molecular mechanisms of microcephaly

> **NIH NIH K22** · UNIVERSITY OF WYOMING · 2020 · $249,000

## Abstract

Project Summary
This proposal seeks to address the molecular mechanisms of autosomal recessive primary microcephaly
(MCPH), a disorder characterized by small brain size and reduced life expectancy. Specifically, it focuses on
the two most commonly mutated genes in MCPH patients, Abnormal Spindle (Asp) and WD Repeat-Containing
Protein 62 (WDR62). A comprehensive, mentored training regimen in both research and career development
has been established in order to ensure success as an independent investigator. First, this proposal uses an
innovative approach in Drosophila melanogaster in order to elucidate the molecular mechanisms of the
disorder, focusing on high resolution analysis of brains at the cell and tissue level using novel genetic &
imaging methods. This phase will require training in fly neurobiology, and a co-mentor who is a leading expert
in the field has been established to serve in this role. Secondly, a novel nuclear function for Asp & WDR62 will
be investigated as the underlying mechanism of MCPH, combining previous graduate training in fly chromatin
biology and gene expression with new training in next-generation sequencing technologies. Both the fly
neurobiology and investigation into the nuclear function of these proteins will build towards the long term goals
of the proposed research, which is to define an `MCPH gene network' that collectively contributes to proper
brain size. This will begin during the mentored phase of the award by generating tools & reagents that will be
critical for success during the independent phase. A genetic modifier screen in the Asp and WDR62 mutant
background will also be carried out to identify candidate genes in the MCPH gene network, establishing a solid
foundation for future work during independence. Additionally, career development will continue throughout the
mentored phase. The NIH provides workshops on mentorship, leadership, grant writing, research ethics and
networking activities which will be completed in parallel with the stated research goals. An advisory committee
has also been established to review research progress, provide constructive feedback on experiments and
guidance on career objectives. Collectively, this training plan in both research and career development will
provide the most comprehensive analysis of MCPH to date and unlock the molecular underpinnings of the
disorder while ensuring success in all phases as an independent investigator.

## Key facts

- **NIH application ID:** 9370205
- **Project number:** 1K22HL137902-01
- **Recipient organization:** UNIVERSITY OF WYOMING
- **Principal Investigator:** Todd Schoborg
- **Activity code:** K22 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $249,000
- **Award type:** 1
- **Project period:** 2020-03-15 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9370205

## Citation

> US National Institutes of Health, RePORTER application 9370205, Investigating the molecular mechanisms of microcephaly (1K22HL137902-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9370205. Licensed CC0.

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