Early last week, Professor Michael Beer, an associate professor of biomedical engineering at Hopkins, was awarded a $1.8 million grant from the National Institutes of Health (NIH) for his work as part of the Encyclopedia of DNA Elements Consortium (ENCODE), a collaboration of 18 labs striving to catalog all coding and regulatory regions of the human genome.
In an interview we The News-Letter, Beer discussed his interests and his work.
Beer has been working at Hopkins for 12 years and was involved in research prior to coming to the University as well. He conducted his post-doctoral research at Princeton University and has extensive experience in computational plasma physics and fusion energy, his previous field of research.
“It soon became clear to me that fusion energy wasn’t going to benefit people in my lifetime,” Beer said. “I wanted to do something else... more socially relevant.”
As a result, he switched over to the field of biomedical engineering.
Currently Beer’s research focuses on the control elements of the genome, such as enhancers, promoters and silencers, that are regions between protein-coding sections of the genome.
Instead of directly being transcribed for protein production, these control elements are shown to have regulatory properties that control cell identity by turning on and off certain genes.
Regulatory regions like enhancers make it possible to switch on the genes that code for a set of proteins specific to a certain cell while switching off the genes that are active in other types of cells in the body. In short such control elements make a cardiomyocyte a cardiomyocyte, and a phagocyte a phagocyte.
In recent years scientists have observed that there is a large heritability to most human diseases. This means that when someone has a disease, the chance of a person in their family having that same disease is significantly higher than the chance of any random person having the disease. Clearly, such a disease has a genomic component.
After delving deeper, researchers were able to map out where many of those heritability components lie in the genome. Surprisingly, almost 95 percent of the variants associated with increased risk of diseases such as stroke, heart disease, Alzheimer’s and some autoimmune diseases are located in certain parts of the genome that do not code for protein. Instead, these variants lie between protein-coding genes in regulatory regions such as enhancers.
Traditional biological techniques have shown a lot about how enhancers work. However, since the sequencing of the genome by the Human Genome Project in 2001, there have been increased attempts at an orthogonal approach that aims to study the entire genome all at once. The type of data that are generated by such large-scale approaches require computational techniques and machine learning in order to analyze the sequence features of the 100,000+ control regions and how these properties allow them to turn on and off genes.
The main biological goal of Beer’s research is to understand how enhancers work, and his lab strives to accomplish this by developing the computational and mathematical methods necessary for researchers like themselves to better understand how enhancers specify cell states and how variations in control regions contribute to common human diseases.
Using these techniques, Beer and his collaborators in the ENCODE project can create models and apply them to explain control element variants and disease heritability. For example, by training their models on a representative data set of enhancers in neurons they can learn what binding sites are important for enhancer function in neurons and whether any detected variants change the binding sites associated with an increased risk for schizophrenia.
When asked to describe his goals for the future, Beer described his hopes to move his research to a deeper and more complex level; Instead of investigating how variants in enhancers change their activity in the genome, he wants to explore how they specifically change cell and tissue behavior and thus the behavior of the entire biological circuit of the human body.
However, he also maintained that the future is difficult to predict and that he is flexible, willing to go whichever way his research takes him.
“The field moves so rapidly, no one knows what’s going to happen next. You don’t know where the next problem is going to lie,” he said.
But he is certain that one of his goals is to continue being at the forefront of computational techniques as well as the experimental methods involved in observing cell interactions and detecting enhancers.
He wants to stay on the interface of medical research, biochemistry, genomics and the exciting new techniques of machine learning.
“What I’ve learned from all my mentors and advisers is that the intersection of fields is where progress really gets made,” Beer said.
