# Cell Surface Receptor Recognition and Membrane Fusion in Mammalian Fertilization

> **NIH NIH K99** · STANFORD UNIVERSITY · 2021 · $127,683

## Abstract

Project Summary/Abstract
 Fertilization is an essential biological process that involves cell surface recognition, adhesion,
and fusion of haploid sperm and egg to form a new, genetically distinct diploid organism. Surprisingly
little is known about how plasma membranes interact and fuse, largely due to the limited availability of
mammalian gametes and the technical challenges of capturing transient extracellular interactions.
While the gamete membrane fusion machinery remains elusive, it is known that a human
immunoglobulin superfamily protein, Izumo1, localizes to the equatorial segment of spermatozoon,
where it interacts with an oocyte ligand, Juno, before gamete fusion takes place. To date, Izumo1-
Juno is the only essential receptor-ligand pair identified in the pathway. Recent genetic studies in
mice have identified additional sperm surface proteins essential for male fertility, but their interactions
and regulation have not been defined.
 To close these major gaps, I have designed a research program around the central hypothesis
that gamete surface proteins orchestrate their structural rearrangements and membrane remodeling,
leading to gamete fusion. I will test my hypothesis by (1) determining the molecular mechanisms of
human Izumo1 self-assembly, (2) characterizing the roles of human Izumo family proteins in
membrane adhesion and fusion, and (3) identifying additional receptor-ligand interactions essential
for gamete fusion and mammalian fertilization. My multidisciplinary approach leverages high-
resolution structural analyses to interrogate the functional organization of known essential gamete
surface proteins, and harnesses high-throughput forward genetic screens to explore the interacting
networks of additional emerging molecules. Crucially, understanding these interactions will elucidate
mechanisms of cell-cell recognition and membrane fusion and reveal essential factors that maintain
human fertility and reproductive health.
 From graduate school, I have extensive training in genetics, cell biology, and membrane
biochemistry. During my early postdoctoral work, I honed my skills in structural biology of cell surface
receptors and protein engineering of viral membrane fusion machines. I will exploit the excellent
research environments in the laboratories of my mentor Dr. Peter Kim and my co-mentor Dr. Chaitan
Khosla and at Stanford University. Under the guidance of my outstanding scientific advisory
committee, I will obtain training essential to mastering enzymology, germ cell biology, and functional
genomics. These research and career-development opportunities will empower me to establish an
independent laboratory to study fundamental questions in the mammalian sperm-egg fertilization
process at the levels of cell biology, mechanistic biochemistry, and structural biology.

## Key facts

- **NIH application ID:** 10190669
- **Project number:** 1K99HD104924-01
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Shaogeng Tang
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $127,683
- **Award type:** 1
- **Project period:** 2021-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10190669

## Citation

> US National Institutes of Health, RePORTER application 10190669, Cell Surface Receptor Recognition and Membrane Fusion in Mammalian Fertilization (1K99HD104924-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10190669. Licensed CC0.

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