# Quantitative super-resolution imaging to map the multi-scale functional organization of cells > **NIH NIH R35** · UNIVERSITY OF PENNSYLVANIA · 2024 · $426,363 ## Abstract Project Summary The long-term goal of this proposal is to understand the mechanisms that regulate sub-cellular organization and the significance of this organization to organelle and cell function. Cells are highly compartmentalized at multiple length scales. At the micron scale, organelles are organized within the cytoplasm and occupy specific sub- cellular zones. Proteins and nucleic acids organize into assemblies at the nanometer scale in the cytosol, nucleus and on cellular membranes to ensure high fidelity of biochemical reactions. This highly orchestrated spatiotemporal organization maintains cellular homeostasis. Not surprisingly, disruptions to the spatiotemporal organization of organelles, proteins and nucleic acids are hallmarks of diseases. In this context, we seek to address three key biological questions: 1. How do molecular assemblies of motor and adapter proteins regulate the transport and spatial positioning of organelles and how are these assemblies disrupted in diseases. 2. How is the molecular identity of organelles such as lysosomes, in turn, linked to organelle positioning and dictate organelle function in health and disease states? 3. What is the cause/consequence relationship between the spatial organization and physical compaction of the genome within the nucleus, the epigenetic modifications, and gene activity? To address these questions, we will take an innovative approach of combining cell biological tools with new, advanced, and quantitative microscopy methods that enable us to visualize the spatial organization of cells in situ and with near molecular spatial resolution. This proposal builds on major advances made by my group in the past 12 years in developing quantitative advanced microscopy tools including quantitative, multiplexed super-resolution microscopy. These methods make it possible to address the molecular scale questions that we are asking in the cell context and with unprecedented quantitative detail. We have used these tools to visualize organelles moving along individual microtubule filaments inside cells, protein nanoplatforms forming on microtubules, inside the cytosol and on organelle membranes, and the folding of the chromatin fiber within the nucleus. These approaches provided new insights into how the microtubule cytoskeleton and motor proteins collectively regulate organelle transport and how the folding of chromatin relates to cell identity under physiological and pathological states. This proposal will build on our advances to elucidate how multiple molecular parts assemble into functional transport units to regulate the positioning and ultimately the function of organelles. We will further map the spatial proteome of these organelles to determine how their molecular identity is linked to organelle positioning and function. Finally, we will seek to address the causal relationship between chromatin structure and function. These areas and our method development integrate synergistically to advanc... ## Key facts - **NIH application ID:** 10762873 - **Project number:** 1R35GM152111-01 - **Recipient organization:** UNIVERSITY OF PENNSYLVANIA - **Principal Investigator:** Melike Lakadamyali - **Activity code:** R35 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2024 - **Award amount:** $426,363 - **Award type:** 1 - **Project period:** 2024-09-07 → 2029-08-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10762873 ## Citation > US National Institutes of Health, RePORTER application 10762873, Quantitative super-resolution imaging to map the multi-scale functional organization of cells (1R35GM152111-01). Retrieved via AI Analytics 2026-06-23 from https://api.ai-analytics.org/grant/nih/10762873. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*