CENTER FOR PHYSICAL GENOMICS AND ENGINEERING AT MCCORMICK SCHOOL OF ENGINEERING

Research

The Center addresses the grand challenge of the physical manipulation of living systems and creation of new strategies for the treatment of disease through the development of macrogenomic engineering, or physical genomics. The ability to reprogram global patterns of gene expression will eventually complement current gene-altering technologies, such as CRISPR-Cas9.

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What is Physical Genomics?

Physical genomics is a new field that involves understanding the structure, function, and fundamental principles of the genome. With this understanding, researchers can develop ways to reversibly regulate, control, and even reprogram global patterns of gene expression. The goal is to be able to impact biological outcomes without altering an organism’s genes themselves.

The impact of physical genomics is expected to be widespread — from treating diseases such as cancer and Alzheimer’s, to regenerative therapies for stroke and heart attack, to improving crop yields and mitigating the impact of climate change on forests and coral reefs.

How Physical Genomics Works

Physical genomics works by regulating chromatin, an intricately folded group of macromolecules including DNA, RNA, and proteins that houses genetic information within cells and whose structure helps to determine which genes get suppressed or expressed.

If we consider genes as analagous to hardware, and chromatin as software, then the structure of chromatin can be thought of as an operating system. If the three-dimensional structure of chromatin changes, it can alter the processing, or transcription, of the information stored in the genes - but it does not alter the genes themselves.

For example, a change in chromatin packing may allow cells to begin expressing certain genes that are normally suppressed (i.e., turning on genes so that wind-chapped skin can rejuvenate itself, or so the liver can break down fats), and vice versa. But this benign power of chromatin can be hijacked when its structure becomes dysregulated. Such changes can eventually manifest themselves as diseases, including cancer, Alzheimer’s, atherosclerosis, and diabetes.

Researchers at the Center for Physical Genomics and Engineering are learning how to control and reprogram this chromatin “operating system” in order to regulate the behavior of cells at a fundamental level. Through a combination of breakthrough superresolution imaging and nanosensing, modeling, and computational genomics techniques they have identified a chromatin packing ‘code’ that has a major role in regulating the transcription process, and thus the characteristic behavior of cells and ultimately, organisms.

The ability to reversibly regulate the three-dimensional structure of chromatin represents a new frontier in biological discovery and has the potential to be one of the major drivers of 21st-century biotechnology.

Macrogenomic Engineering

The tools developed at the Center have the potential to open new fields of biological research, lead to new strategies for treatment of disease, and enable adaptive engineering of plants and animals to meet environmental challenges.  For example, the ability to manipulate cells can lead to the development of a principally new, physics-based anti-cancer strategy that may prevent the emergence of tumor cell resistance to anti-cancer therapies.  Prevention of chemoresistance will overcome the primary reason for treatment failure of most cancer patients.

MGE strategies could also be deployed to address other diseases in which global genomic reprogramming plays a role such as Alzheimer’s disease, atherosclerosis, and developmental diseases.

Beyond medicine, MGE may find application in fields as diverse as synthetic biology, where it would be advantageous to modulate cell functionality to increase specific outputs, and in agriculture, to enhance global gene expression states associated with crop acclimation in response to changing environmental conditions. The Center will establish the foundations of this new field of engineering.