{"id":2080,"date":"2005-09-16T11:21:16","date_gmt":"2005-09-16T15:21:16","guid":{"rendered":"https:\/\/engineering.jhu.edu\/magazine-archive\/?p=2080"},"modified":"2014-12-16T11:22:00","modified_gmt":"2014-12-16T16:22:00","slug":"drivers-seat-single-cell","status":"publish","type":"post","link":"https:\/\/engineering.jhu.edu\/magazine-archive\/2005\/09\/drivers-seat-single-cell\/","title":{"rendered":"In the Driver\u2019s Seat of a Single Cell"},"content":{"rendered":"

Navigating via computer-based mathematical models, Pablo A. Iglesias aims to understand\u2014and regulate\u2014how cells move and divide.<\/strong><\/p>\n

Call him a control freak, but Pablo A. Iglesias covers more ground than you can imagine in his efforts to direct the movement of cells. Iglesias is steering his considerable knowledge of control engineering down a new path in cell biology that could well lead to extraordinary discoveries.<\/p>\n

A professor in the Whiting School\u2019s Department of Electrical and Computer Engineering, Iglesias has joint appointments in the departments of Biomedical Engineering and Applied Mathematics and Statistics. That\u2019s a testament to his own flexibility in pursuing a path. The Venezuelan native earned his doctorate in control engineering at Cambridge University in 1991.<\/p>\n

Control engineering is the study of automatic regulating systems, which often take the form of small devices silently managing mechanisms and household appliances. From thermostats to cruise controls, these control systems perform surprisingly sophisticated and dynamic tasks. But they\u2019re nothing new. To make that point, Iglesias turns the clock back to 1903 and the Wright Brothers. \u201cIn fact, their greatest contribution to flight wasn\u2019t the aircraft itself,\u201d he notes, \u201cbut the control system that allowed them to fly the craft, which is control engineering.\u201d<\/p>\n

Today\u2019s control engineers employ not bike chains and canvas but computer-based mathematical modeling systems in order to test-drive controllers in theory before they are actually engineered. Employing the principles of control theory, the control engineer studies and adjusts a mathematical model to create a predictable set of variable responses within a dynamic system.<\/p>\n

Pedaling on the Biological Signaling Pathways<\/strong><\/p>\n

For Iglesias and his team at the Cellular Signaling and Control Laboratory, the challenge is applying this discipline to the study of biological signaling pathways, the amazingly complex regulatory system within the human body. \u201cAt the simplest level, it\u2019s everything that happens inside a single cell that regulates its well-being,\u201d says Iglesias. From body temperature to cholesterol counts, \u201cNo matter the scale, all of the body\u2019s processes are very tightly regulated along much the same lines as apply to control engineering.\u201d<\/p>\n

First fascinated by this parallel seven years ago, Iglesias now focuses on two aspects of biological signaling pathways at the cellular level. The first investigation in his laboratory involves the study of chemotaxis, the movement of single cells, or even larger multicellular organisms, in response to the introduction of certain chemicals into their environment. For example, human white blood cells will pursue and destroy invasive bacteria, but only because a bacterium secretes a particular chemical detected by certain sensors on the cell.<\/p>\n

In particular, Iglesias seeks to understand a human cell\u2019s biochemical \u201cguidance system\u201d in terms of how it regulates chemotaxis. \u201cRight now, we\u2019re specifically investigating the possibility of feedback loops,\u201d he says. \u201cWe have a mathematical model that shows that some of a cell\u2019s observed behavior can be explained by these feedback loops, which measure an outside chemical concentration, produce a response, and then feed it back to the cell\u2019s sensors.\u201d The next step in this study, says Iglesias, will be to move from modeling a cell\u2019s guidance mechanism to developing models of how the cell\u2019s actual locomotion takes place.<\/p>\n

\"By<\/a>
By creating computer models, Pablo A. Iglesias studies the control dynamics of Dictyostelium, a single-celled organism whose movements are similar to the human white blood cell. The illustration shows the theoretical prediction (top) and experimental result of simultaneous stimulation of the cells.<\/strong><\/figcaption><\/figure>\n

Inside a Cellular Split<\/strong><\/p>\n

In a second study, Iglesias and his team are investigating the control dynamics of cell division\u2014and the steps that must occur for a cell to divide successfully. Following division, the resulting two daughter cells must each contain an equal half of the chromosomes from the original cell. However, if these genetic materials are not distributed equally, a condition called aneuploidy occurs. Iglesias notes that aneuploidy is one of the leading causes of genetic disease and cancer.<\/p>\n

To gain a greater insight into the control mechanisms governing successful cell division, Iglesias and his colleagues are creating models to analyze cytokinesis, the final step in cellular division, where the two new daughter cells actually separate. To test for the presence of a feedback loop in the cell during this process, Iglesias collaborates with researchers at the Johns Hopkins School of Medicine\u2019s Department of Cell Biology. Together they are developing an apparatus to be used during cell division\u2014a dual micropipette aspirator that can apply pressure to cells through a microneedle less than five microns wide. \u201cWhen a cell is dividing, we will actually apply some force to it that works against its division,\u201d says Iglesias. \u201cWhat we think is going to happen is that the cell will then push harder to divide itself. Just like a thermostat that works harder when a window is left open, the cell\u2019s feedback mechanism will kick in to correct the discrepancy.\u201d<\/p>\n

Down the Road: Controlling Disease<\/strong><\/p>\n

All of this research, while purely theoretical, has the potential for providing substantial results. For example, malignant tumors in the human body spread through chemotaxis, as do certain other diseases. Short-circuiting the process of how these chemical cues work could effectively halt the progress of such diseases. And, as Iglesias points out, studying cell division shines the light on promising developments in fighting cancer. \u201cA number of the cancer treatments currently being tried are attempting to disrupt cell division in cancer cells,\u201d he says. \u201cSo understanding the control system of cell division actually may lead to some treatment.\u201d<\/p>\n

The approach Iglesias takes has earned high praise from his colleagues. \u201cThe work he is doing is simply fantastic,\u201d says Gerard G. Meyer, professor and chair of Electrical and Computer Engineering. \u201cThe promise of his research is enormous, in terms of understanding those biological control mechanisms that govern the onset of disease\u2014and its possible prevention.\u201d<\/p>\n

Typically, Iglesias\u2019s response is modest. \u201cI\u2019m often asked why I look at cell biology problems if I\u2019m in electrical engineering,\u201d he says smiling. \u201cMy answer is that I find it interesting. The knowledge that I have in systems theory traditionally has not been used in biology. So there are a lot of open problems where I think I can make a contribution.\u201d<\/p>\n

For more on Pablo A. Iglesias\u2019s laboratory, visit www.ece.jhu.edu<\/strong><\/p>\n

\"Iglesias<\/a>
\u201cNo matter the scale, all the body\u2019s processes are very tightly regulated along much the same lines as apply to control engineering,\u201d notes Iglesias. Liu Yang, a PhD student in Electrical and Computer Engineering, works with Iglesias.<\/strong><\/figcaption><\/figure>\n","protected":false},"excerpt":{"rendered":"

Navigating via computer-based mathematical models, Pablo A. Iglesias aims to understand\u2014and regulate\u2014how cells move and divide. Call him a control freak, but Pablo A. Iglesias covers more ground than you can imagine in his efforts to direct the movement of cells. Iglesias is steering his considerable knowledge of control engineering down a new path in…<\/p>\n","protected":false},"author":4,"featured_media":2086,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[84],"tags":[],"class_list":["post-2080","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-high-perfomers","issue-fall-2005"],"acf":[],"yoast_head":"\nIn the Driver\u2019s Seat of a Single Cell - JHU Engineering Magazine<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/engineering.jhu.edu\/magazine-archive\/2005\/09\/drivers-seat-single-cell\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"In the Driver\u2019s Seat of a Single Cell - JHU Engineering Magazine\" \/>\n<meta property=\"og:description\" content=\"Navigating via computer-based mathematical models, Pablo A. 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