Student Helper for Organelle Segmentation

Clinical studies have indicated that the progression of acute myeloid leukemia (AML) is strongly associated with platelet defects. This suggests that qualitative dysfunction of platelets in AML may be related to ultrastructural alterations that occur during disease progression. Our proposed research aims to better understand and visualize the platelet cellular structures that exist during the development of AML and provide a basis for developing early non-invasive diagnostics with enhanced sensitivity, reliability, and speed compared to current methods. To this end, we will employ cutting edge cryo-electron tomography (cryo-ET), an experimental technique that uses a transmission electron microscope to image frozen, hydrated platelets, thereby revealing native subcellular morphology with nanometer resolution of fine structural details. In preliminary studies, we recently demonstrated the ability to use this technique to perform per-cell organelle identification, with quantitative measurements of organelle shape and distribution. With this approach, we observed internal platelet changes in the mouse model of AML, including organelle depletion and an overall decrease in platelet cell size relative to control cells. Critically, we were able to detect abnormal organelles with unique morphologic changes at an early stage of AML, before these abnormalities could be uncovered by a Complete Blood Count (CBC) test. We, therefore, hypothesize that these changes may represent potential bioimaging markers that can be leveraged to provide early diagnosis of AML. In this proposal, we aim to determine if similar morphological changes are present in platelet organelles from AML patients.