What can machines tell us about ourselves?
UND researcher Manu finding answers about cell identity and regeneration
The idea of machines becoming indistinguishable from humans has been a storyline in science fiction movies for decades. But what if humans really do have something in common with a technology they invented?
UND Assistant Professor of Biology Manu (who has a single name) is using his knowledge of seemingly unconnected scientific disciplines to better understand how cells regenerate and determine what types of cells they’ll become. How cells make decisions in response to their environment has similarities to the way computers operate, he said.
“Our lab studies the process of blood cell regeneration,” Manu said. “Every day, about 200 billion of our blood cells die. To maintain our functions, the body generates 200 billion new red and white blood cells daily.
“In our bone marrow, we have special cells called hematopoietic stem cells with the capability of self-renewing,” he added. “When they divide, they make a new copy of themselves. That’s how over our entire lifetimes, we continue to regenerate billions of blood cells every day.”
More specifically, Manu is studying the internal logic of how progenitor cells such as hematopoietic stem cells respond to the body’s signals about how to react in different situations.
“For example, when we are sick, our bone marrow needs to generate more white blood cells – immune cells that fight infection,” he said. “We are studying how hematopoietic stem cells make these decisions of choosing to become a red blood cell or a white blood cell.”
Cellular on and off switches
Manu compares this decision-making process within stem cells to the circuitry used in digital computers, including laptops and smart phones.
“It’s not unlike a computer because we have genes make special proteins called transcription factors that instruct other genes to turn on and off,” he said. “These special genes sense the body’s signals and turn on the genes that define a red blood cell or a white blood cell, similar to how transistors in computers turn other transistors on or off to process data.”
This research into the basic biology of hematopoiesis could contribute to the development of an effective treatment for leukemia, which accounted for nearly 23,000 deaths in the United States last year.
“Leukemias are a disease where the circuitry of genes turning on and off – these ones and zeroes – go haywire,” Manu related. “You have mutations, many of them in the special genes that instruct other genes, and that’s where cancers start. Sometimes, what these mutations do is turn off or turn on a gene in the wrong cell at the wrong time.”
Perhaps 10 to 20 years into the future, Manu believes that the insights from this basic research could also help advance the field of regenerative medicine, which aims to grow new body organs to solve the problem of the immune system rejecting transplanted organs.
“The long-term hope in this field is that we could take cells from the host and reprogram those cells – tell them to differentiate into stem cells – and then grow organs from their own cells.” he explained. “In that case, there would be no graft rejection because those cells are derived from the patient themselves.”
NSF CAREER Award
Earlier this year, Manu became the third UND researcher in the past 10 years to receive a research award from the National Science Foundation’s (NSF) Faculty Early Career Development (CAREER) Program. The grant for basic research is for $865,269 over five years. It’s considered one of NSF’s most prestigious awards and is intended to support early-career faculty who have the potential to serve as academic role models in research and education, as well as to lead advances in the mission of their department or organization.
“The NSF CAREER award is a major accomplishment for Manu and an honor for his department, the College of Arts & Sciences, and UND,” said John Mihelich, UND vice president for research and economic development.
In India, Manu earned an undergraduate degree in physics, but when he came to the United States for his graduate studies, he wanted to change fields. At Stony Brook University in New York (SUNY), he met his future Ph.D. advisor, who was doing research that attracted Manu’s interest.
“They were using techniques from physics, mathematics and engineering to study how embryos develop,” he said. “A human develops from a featureless single-cell zygote into an intricately patterned, fully formed individual. How you get a pattern from no pattern is an amazing and mysterious process. They used and combined these disparate fields to approach this challenging question, which was very appealing to me.”
Manu received his Ph.D. in applied mathematics and statistics from SUNY, focusing on using mathematic equations to describe the process of development. He did his postdoctoral work in ecology and evolution at the University of Chicago. In 2014, he accepted a position with the UND Department of Biology, where he collaborates with a team of developmental biologists and biochemists in the School of Medicine & Health Sciences.
Student opportunities in systems biology
Manu said his lab is unique in the nation because it uses techniques from mathematical models, computer science and electrical engineering to describe the developmental process of genes turning on and off to show how cells make decisions.
“To understand this process, we have a wet lab where people are doing experiments with cells, DNA, RNA and so on – the usual things a molecular biology lab would do,” he said. “But we also use techniques from big data science, machine learning and super-computing. We run our models on the University’s big computer clusters.”
Manu’s students can choose to be experimental biologists, theoretical biologists or both.
“We have students who choose to do both and combine them where they may develop a model and then make some predictions from the model,” he said. “If you turn off this gene, what will the outcome be? They can make the prediction in silico and then go in the lab to do those kinds of experiments.”