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Beta cell adaptation mechanisms during caloric restriction and ER stress

US · IL NIH grant awarded #nih-5R01DK138141-03

Summary

This project investigates how beta cell epigenetic, transcriptional, functional, and longevity landscapes are affected by metabolic modulation (diet, aging, ER stress) and explores the spatial organization of the beta cell (epi)genome in 3D, aiming to understand beta cell adaptation and health in Type 2 Diabetes and aging.

What they want

The overarching goal is to investigate how beta cell epigenetic, transcriptional, functional, and cell longevity landscapes are affected by metabolic modulation introduced by changes in diet composition (e.g., calorie restriction (CR), high-fat diet), or during aging and/or ER stress. Additionally, the project will investigate fundamental aspects regarding the spatial (in situ) organization of the beta cell (epi)genome in 3D, and how this aspect correlates with heterogeneous gene transcriptional patterns. Experiments will leverage single cell multiome transcriptomics, high-resolution light, electron and stable-isotope microscopy, and quantification of in vivo beta cell function to determine spatial, molecular, and functional landscapes of mouse and human beta cells exposed to different metabolic challenges.
Deliverables
  • Understanding of beta cell epigenetic, transcriptional, functional, and cell longevity landscapes under metabolic modulation, aging, and ER stress
  • Investigation of the spatial (in situ) organization of the beta cell (epi)genome in 3D
  • Correlation of spatial organization with heterogeneous gene transcriptional patterns
  • Insights into how beta cells adapt to changes in metabolic demands and/or ER stress
  • New ways to promote and/or preserve beta cell function in aging patients and those with T2D
Technical requirements
  • Single cell multiome transcriptomics
  • High-resolution light microscopy
  • Electron microscopy
  • Stable-isotope microscopy
  • Quantification of in vivo beta cell function
  • Use of mouse beta cells
  • Use of human beta cells

Market context

inferred from NAICS
Professional, Scientific & Technical Services
NAICS 541714
US market size
$2.0T
Typical award
$25K – $50M
Typical buyers
All federal civilianDoDStates
Commonly required
8(a)WOSBSDVOSBPE/PMP

Sector-level estimate — full code lookup not yet in catalog.

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