Photonics probing of DNA mass density spatial structure for cancer diagnostics

用于癌症诊断的 DNA 质量密度空间结构的光子学探测

基本信息

批准号：
10196725
负责人：
Prabhakar Pradhan
金额：
$ 39.74万
依托单位：
MISSISSIPPI STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-04-02 至 2024-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10196725
关键词：
Affect Americas Biological Biological Markers Biological Sciences Biophysics Breast Cancer Detection Cancer Diagnostics Cancerous Cell Culture Techniques Cell Nucleus Cells Cellular Structures Communities Computer software Confocal Microscopy Coupled Coupling Cytoskeleton DNA DNA Binding DNA Probes DNA Sequence Alteration DNA Structure Data Detection Development Dimensions Disease Disease Progression Dyes Fluorescence Microscopy Fluorescent Dyes Gene Rearrangement Goals Heterogeneity Human Image Institutes Journals Lasers Lead Length Light Liver Malignant Neoplasms Measurement Measures Methods Molecular Morphology Mutation Normal Cell Nuclear Nuclear Structure Optics Organelles Outcome Physics Physiological Process Property Prostate Publishing Refractive Errors Refractive Indices Research Research Design Research Personnel Resolution Sampling Scanning Series Skin Slice Societies Spectrum Analysis Stains Statistical Data Interpretation Structure System Techniques Thinness Tissue Sample Tissues Tumor Cell Biology Tumorigenicity Validation Variant Work base cancer biomarkers cancer cell carcinogenesis cell type cellular imaging condensed matter physics confocal imaging density indexing microscopic imaging molecular mass nano nanoscale neglect news novel optical lattices photonics physical state skeletal submicron success tool user-friendly

项目摘要

Abstract Cancer is known to be associated with genetic mutations. Evidences suggest that these genetic changes lead to increased structural disorder in biological cell nuclei. This disorder is believed to result from alteration and rearrangement of DNA molecular mass density at the beginning. In the case of progressive carcinogenesis, such changes occur at length scales ranging from nano- (<100nm) to submicron (>100nm) scales. Consequently, it has been recognized that measurement and quantification of these structural changes could, therefore, be a potential cancer biomarker. Accordingly, some recent studies based on partial wave spectroscopy and other nano-optical techniques have quantified the nanoscale structural properties in cells. However, these techniques are still in the early stages and require complicated new experimental setup, thus limiting access to these studies to only a handful of research groups in the biomedical and biological sciences. Meanwhile, the use of existing optical techniques, e.g., confocal microscopy, to conduct such studies is still unexplored. In view of that, we have developed a novel method, by combining confocal microscopy imaging and a technique borrowed from mesoscopic physics, termed as inverse participation ratio (IPR) technique, or simply the “IPR technique”, to measure and quantify the degree of structural disorder in cell nuclei. Components of the cellular matrix are highly heterogeneous, including multifractality of dimensions, e.g., cellular structures formed at different scales. Thus, to interrogate cellular heterogeneity and to obtain quantitative data about structural or DNA molecular morphological disorder (from the norm), it is generally necessary to establish a number of parameters. However, with the present IPR approach it is possible to selectively quantify structural changes in the nuclear DNA, by using DAPI stained confocal micrographs, and represent it in just one single parameter, namely the <IPR> value. The <IPR> value provides a measure of the degree of structural disorder, i.e., “disorder strength”, of the sample. Our preliminary results show an underlying relationship between structural disorder in nuclear DNA and carcinogenesis. Therefore, in this proposal, we will measure and quantify the submicron-scale structural disorder in the nuclear DNA of different normal and cancerous cells, obtained from cell cultures and tissues, via IPR analysis of the confocal micrographs. By coupling the IPR technique to the widely used confocal microscopy, we aim to (i) develop an automated quantification technique to measure the degree of structural disorder of selective molecular density in an organelle, in particular nuclear DNA, from DAPI stained confocal micrographs of the cells, and (ii) calibrate the degree of structural disorder in normal and cancer cells in liver, skin, and skeletal cell cultures and tissues nuclear structure. The success of this project will lead to a new direction in cancer detection, as well as cell characterization based on quantified structural changes in nuclear DNA.

抽象的已知癌症与基因突变有关。证据表明这些遗传变化引导生物细胞核中结构障碍的增加。人们认为这种疾病是由于改变而引起的 DNA分子质量密度在开始时的重排。在进行性癌变的情况下，从纳米 - （<100nm）到亚微米（> 100nm）尺度的长度尺度发生变化。因此，它因此，已经认识到，这些结构变化的测量和数量可能是潜在的癌症生物标志物。根据某些人，一些基于部分波光谱和其他基于部分波光谱的研究纳米光学技术已经量化了细胞中的纳米级结构特性。但是，这些技术仍处于早期阶段，需要复杂的新实验设置，从而限制了对这些研究的访问在生物医学和生物学科学中只有少数研究小组。刻薄的是，现有的使用进行此类研究的光学技术，例如共聚焦显微镜仍然是出乎意料的。鉴于这一点，我们有通过结合共聚焦显微镜成像和一种从中借来的技术来开发了一种新颖的方法介质物理学，称为反参与率（IPR）技术，或仅仅是“ IPR技术” 测量和量化细胞核中结构障碍的程度。细胞基质的成分高度异质性，包括维数的多纹状体，例如在不同尺度形成的细胞结构。那，询问细胞异质性并获得有关结构或DNA分子的定量数据形态障碍（从规范中）通常有必要建立许多参数。然而，通过当前的IPR方法，可以通过使用DAPI染色的共聚焦显微照片，并仅以一个单个参数表示它，即<ipr>值。 <ipr>值提供了样本的结构障碍程度，即“混乱强度”的度量。我们的初步结果表明核DNA结构障碍与致癌作用。因此，在此提案中，我们将测量和量化亚微米尺度的结构障碍在不同正常和取消细胞的核DNA中，通过IPR从细胞培养物和组织获得共聚焦显微照片的分析。通过将IPR技术耦合到广泛使用的共聚焦显微镜，我们旨在（i）开发一种自动数量技术来衡量选择性的结构性障碍程度来自DAPI的细胞器中的分子密度，特别是核DNA，染色细胞，以及（ii）校准肝脏，皮肤和骨骼细胞中正常和癌细胞中结构障碍的程度培养和组织核结构。该项目的成功将导致癌症检测的新方向以及基于核DNA的定量结构变化的细胞表征。

项目成果

期刊论文数量（2）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Photonics probing of pup brain tissue and molecular-specific nuclear nanostructure alterations due to fetal alcoholism via light scattering/localization approaches.

DOI：
10.1117/1.jbo.27.7.076002
发表时间：
2022-07
期刊：
JOURNAL OF BIOMEDICAL OPTICS
影响因子：
3.5
作者：
Adhikari, Prakash;Shukla, Pradeep;Alharthi, Fatemah;Bhandari, Shiva;Meena, Avtar;Rao, Radhakrishna;Pradhan, Prabhakar
通讯作者：
Pradhan, Prabhakar