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<title>Research | Beliveau Lab</title>
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<h1>Research</h1>
<p class="lead">Each human nucleus contains two meters of DNA packaged into an organelle a mere ~10 µm in diameter. Despite this dramatic difference in scale, the three-dimensional organization of the genome is non-random and plays a critical functional role in both health and disease. Our laboratory uses a combination of computational, molecular, and optical approaches to investigate the causes and consequences of 3D genome organization in single cells.</p>
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<div class="research-card"><img class="research-fig" src="images/research/1_imaging.png" alt="Imaging chromosome structure at the nanoscale" loading="lazy"><h3>Imaging chromosome structure at the nanoscale</h3><p>We use multiplexed <a href="https://www.nature.com/articles/ncomms8147.pdf" target="_blank" rel="noopener">DNA-PAINT and STORM</a> single-molecule super-resolution microscopy in combination with programmable <a href="http://www.pnas.org/content/pnas/109/52/21301.full.pdf" target="_blank" rel="noopener">Oligopaint</a> FISH probes to visualize the nanoscale structure of chromosomes. This approach provides a ~10-fold improvement in resolution compared to conventional microscopy and allows us to map the conformation and folding of chromosomes with exquisite detail.</p></div>
<div class="research-card"><img class="research-fig" src="images/research/2_dynamics.png" alt="Visualizing chromatin dynamics" loading="lazy"><h3>Visualizing chromatin dynamics</h3><p>We are interested in dynamic and structural properties of chromosomes in live cells. We use advanced live-cell imaging approaches such as single-particle tracking, fluorescence correlation spectroscopy, and super-resolution imaging to investigate the behavior of chromosomes in vivo.</p></div>
<div class="research-card"><img class="research-fig" src="images/research/3_sptx.png" alt="Spatial transcriptomics" loading="lazy"><h3>Spatial transcriptomics</h3><p>Technologies such as single-cell RNA sequencing are producing a wealth of information about cell populations in different tissues during and after development. Determining the spatial arrangement of these cells remains much more challenging. We deploy our <a href="https://www.biorxiv.org/content/early/2018/08/27/401810" target="_blank" rel="noopener">SABER multiplexed imaging technology</a> in combination with advanced microscopy to map patterns of gene expression in their native contexts.</p></div>
<div class="research-card"><img class="research-fig" src="images/research/4_screening.png" alt="High-throughput screening" loading="lazy"><h3>High-throughput screening</h3><p>We are interested in deploying high-throughput approaches such as <a href="http://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1002667&type=printable" target="_blank" rel="noopener">Hi-FISH</a> and targeted mass spectrometry to identify the molecular factors that shape and structure the 3D genome.</p></div>
<div class="research-card"><img class="research-fig" src="images/research/5_mining.png" alt="Genome mining and thermodynamic modeling" loading="lazy"><h3>Genome mining and thermodynamic modeling</h3><p>We build and use <a href="http://www.pnas.org/content/pnas/early/2018/02/16/1714530115.full.pdf" target="_blank" rel="noopener">computational tools</a> to find optimal sites for molecular reagents such as in situ hybridization probes on a genome-wide scale. We also use machine learning and analytical computing to predict the thermodynamic behavior of nucleic acid systems and to investigate the sequence and structural properties of the genome.</p></div>
<div class="research-card"><img class="research-fig" src="images/research/6_techdev.png" alt="Genomics technology development" loading="lazy"><h3>Genomics technology development</h3><p>We develop new <a href="http://www.pnas.org/content/109/52/21301" target="_blank" rel="noopener">enabling molecular technologies</a> to allow researchers to investigate a broad range of questions involving genome organization and gene expression.</p></div>
<div class="research-card"><img class="research-fig" src="images/research/7_microscopy.png" alt="Advanced microscopy and instrumentation" loading="lazy"><h3>Advanced microscopy and instrumentation</h3><p>Multiplexed super-resolution imaging of chromosomes in their in situ context presents significant technical challenges. We design and build <a href="https://www.nature.com/articles/s41467-017-02028-8.pdf" target="_blank" rel="noopener">custom optical configurations</a> and apply advanced optical methods to increase our ability to visualize genome organization in single cells.</p></div>
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