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How do human cells communicate?
Twitter. Snapchat. A conference call. A wink. A bear hug. People communicate with each other in many ways, depending on who they are connecting with, and what information they want to convey. Human cells communicate using different modalities too, with staggering complexity during processes of growth, differentiation, and regeneration.
How a cell switches modes of communication, and multiple cells work together to coordinate behavior at the tissue level are unsolved questions. Broadly, cell communication can be classified as biochemical, mechanical or electrical communication. To pull off the engineering feat of forming new tissue, whether in health or disease, cells employ all three modes. Uncovering "the design principles, rules and decisions" human cells use to communicate during growth, and using this information to impact human health, is a fundamental goal of the Qutub Lab.
Building blocks of communication 100,000s proteins & genes, and multiple sources of electrical and mechanical forces can contribute to a cell's communication with its neighboring cells. In turn, millions of diverse cells organize to form growing tissues.
Dynamics of communication Cells change how they communicate when stressed or hungry, and limited oxygen is a good way to stress out cells. We're interested in understanding cell communication in cells growing in the brain and bone marrow, where tissue is acutely sensitive to hypoxic and metabolic changes.
What can seem like an intractable engineering puzzle, can be approached by developing tools that enable a quantitative, mathematical understanding of cell communication.
The triad approach of combining theory-driven modeling, data science and live imaging experiments on human cells allow us to characterize cell communication from multiple perspectives, test our theories experimentally, and ask whether there is link between changes in cell function and human health measured at the systems level. To enable this approach, lab members herald from diverse disciplines (e.g., computer science, neuroscience, math, chemical engineering), all focused on the common goal of deciphering how cells communicate during development, growth and regeneration.
How do cells form brain tissue?
Two of the most complex and conceptually beautiful examples of cells changing their modes of communication are the formation of neurons from stem cells and the formation of new blood vessels aligning the nerves during development, repair, and regeneration.
We're discovering how cell communication changes during network formation - both neural network and vascular networks. Understanding the formation of living networks is a key to interpreting how information is passed between cells dynamically - essentially how cells learn to learn.
Human Neural Networks
Day 24, Cells (A. Mahadevan, Qutub Lab 2018)
Red: Neurofilament, Blue: DAPI, White: Ki67, Green: Nestin
How do blood cells grow cancerous?
Some of the same protein pathways that help stem cells form brain tissue, also induce blood stem cells to become malignant. Characterizing how these pathways work differently in different contexts - and in different people - is leading to the discovery of potential new chemotherapy targets, and re-purposing of drugs tailored to individual patients.
To achieve this, we develop computational methods to interpret the "molecular language" of cells. An analogy is the cancer cells in the blood are communicating to their neighbors using words from a foreign language, and communication cues are misread. We are uncovering the language used by healthy cells, the jumbled words used by the cancerous cells, and how this communication at the molecular level leads to malignancy.
How are we using knowledge gained about
cell communication to impact society?
Understanding how neurons form, how cells organize as they grow into new capillary networks, how blood cells become malignant - these are fundamental biological questions that drive the Qutub Lab's quest to uncover engineering principles of human cell communication.
When answered, these are also questions that can transform how we characterize, maintain, and improve human health. Functional regeneration of the brain's neural cells and neurovasculature would open new avenues to treating developmental brain disorders and neurodegenerative diseases like stroke and Alzheimer's, while identification of new signatures for leukemia is leading to new diagnostics and potential therapies for pediatric and adult blood cancers.
Clinical Impact To bridge the gap between the lab's basic science and clinical impact, we work closely with clinical collaborators and design studies with human volunteers and patients where we can directly ask whether cellular changes are indicative of changes in whole body health or disease progression.
Technological Impact To answer the biological questions, we also innovate in the design of new experiments, new algorithms to classify images and high-dimensional biological data, and interactive software that we make available to the public for use in interpreting their data and images.
Restoring human health
Modeling methods we have developed are being used to interpret quantitative, molecular hallmarks of cancers and neurodegenerative diseases, design new clinical trials, and identify potential new therapies. Read about translational applications of our work, explore the Leukemia Atlases online, or volunteer for one of our health-tracking studies.
How do daily behaviors affect cell health & communication?
Many of our studies look at how single cells behave or how multiple human cells communicate together, where we ask fundamental questions about how neural, vascular or cancerous tissue forms. At the same time, we have been studying health outcomes of the volunteers and patients in our studies.
Our newest work bridges the gap from "systems" to "cell": we are developing methods and models to test our theories of how daily behaviors impact cell level processes.
Designing new tools & algorithms
We develop tools to characterize biological communication on all scales (molecular, cellular, tissue, organ, social, etc.), and interpret the accompanying experimental and health data. Read about the Atlases & models, algorithms, and software we develop here.
Real-time modeling of health
Three years ago we began our first studies to develop predictive algorithms of daily behaviors (e.g., sleep duration) from health and social data obtained non-invasively (e.g., by wearable devices).