CENTER FOR PHYSICAL GENOMICS AND ENGINEERING AT MCCORMICK SCHOOL OF ENGINEERING

The Implications of Physical Genomics

Just as the emergence of genetic engineering has provided the power to genetically manipulate cell function, macrogenomic engineering, also known as physical genomics, has the potential to power the physical manipulation of living systems and create new strategies for treatment of disease, agricultural development, and climate change adaptation, among other  applications.

Physical genomics-based strategies may be employed to address diseases where global genomic reprogramming is involved, such as cancer, Alzheimer’s, and atherosclerosis, and be leveraged for other medical applications such as the controlled regeneration of heart tissue after an infarction or of neurons after a stroke. In the non-medical realm, the ability to reversibly regulate global patterns of gene transcription could lead to improved crop adaptation to changing climates, help coral reefs adapt and thrive in warming oceans, and lead to new classes of biofuels and biomaterials. Indeed, applications of physical genomics can be envisioned for a wide range of living systems. It is the mission of the Center for Physical Genomics and Engineering to establish the foundations of this powerful new field and develop a framework to translate its discoveries into technologies and treatments that benefit humanity.

Proof of Concept: An Exciting New Approach to Cancer Treatment

One of the primary initial applications of the convergent physical genomics and engineering technologies developed at CPGE is cancer therapeutics. CPGE researchers are targeting chromatin packing structure in the nucleus in order to limit cancer cells' ability to adapt and evolve resistance to chemotherapeutic drugs, with a goal of increasing their lethality and reducing side effects.

This technique, called Chromatin Protection Therapy (CPT), has produced promising preliminary results. When used in combination with current chemotherapy drugs in both laboratory cell cultures and living animal models, the technique eliminated virtually 100 percent of cancer cells in seven different types of malignancies, with no effect on non-cancer cells.

While developing Chromatin Protection Therapy techniques, our researchers discovered that the packing density of chromatin in cancer cells produces predictable changes in gene expression. The more heterogeneous and disordered the packing density, the more likely cancer cells were to survive, even in the face of chemotherapy. The more ordered the packing density, however, the more likely the cells would die from cancer treatment. By physically regulating the density of chromatin structure, the cancer cell’s ability to adapt and evade chemotherapy was also regulated - potentially making these drugs far more effective as a treatment, even at substantially lower doses.

CPGE researchers found that one way they could manipulate chromatin packing structure is by changing the electrolytes present in the cell’s nucleus. The team screened multiple existing drug compounds to find promising candidates that could alter the physical environment inside nuclei and thus modulate the spatial arrangement of chromatin packing density. Two of the drugs the team pinpointed are FDA-approved immunological agents, already on the market, that physicians prescribe for arthritis and heart conditions, respectively, and both have now been found to have a side effect of altering chromatin packing density.

As research continues, CPGE scientists are identifying additional synergistic compounds and learning more about the relationship between chromatin packing density and gene expression, disease initiation and progression, and response to treatment. As our understanding of these fundamental processes grows and ever more powerful tools are developed by our researchers, the potential for new treatments that will impact patients with cancer - and other diseases - becomes greater with each new discovery.

Fighting Cancer's Resistance to Treatment

Future Potential Impact Areas

As all biological entities are ultimately defined by their genome, applications may be found in virtually all living systems.

Medicine

Alzheimer’s disease, diabetes, atherosclerosis, non-toxic therapies, neurological recovery after stroke, regeneration of cardiac tissue after a heart attack

Synthetic Biology

Modulating cell functionality to increase specific outputs

Agriculture

Improved crop yields, adaptation to regional environmental shifts

Climate Change Management

Coral reef adaptation to warmer ocean temperatures, improved biodiversity