Gene regulation: Controlling cells to improve medical treatments

Gene regulation has become a key focus of scientific discovery since scientists first cracked the code of DNA, unraveling the intricate sequence of molecules that dictate our cells’ behavior. But DNA, while pivotal, is only half of the story.

Our bodies consist of numerous cell types, from skin to muscle to brain cells, all containing the same DNA. Yet, the question remains: how does each cell know when to become skin, muscle, or brain cells?

Complex blueprint of DNA

Picture DNA as a long, twisted ladder, packed with billions of tiny building blocks. It carries the precise instructions that guide the growth, function, and repair of our bodies. When unraveled, this ladder can stretch up to two meters long, much too long to fit within the tiny confines of a cell.

Chromatin, a complex of DNA and proteins, solves this problem by packaging the DNA into a condensed, organized structure that fits within the cell nucleus.

It functions like beads on a string, looped and packed into chromosomes, which allows DNA to be assembled in a small area and unpacked whenever the cell needs access to genetic information.

In this complex code, DNA contains both coding and non-coding sequences. Coding DNA, or genes, supply the instructions for building proteins, the essential cellular building blocks and mediators. Non-coding DNA plays a pivotal supporting role in controlling when and how these genes are switched on or off to form proteins.

Role of chromatin in gene regulation

Chromatin organization is crucial to the process of gene regulation. Tightly packed chromatin restricts access to genes, keeping them off. In contrast, loosely packed chromatin allows genes to be turned on and expressed.

Although all humans inherit a fixed set of genes, their expression can vary widely due to factors such as diet, stress, and exposure to pollution.

This phenomenon, known as epigenetics, controls the identity and function of cells, thus shaping the cell’s destiny.

Emerging frontiers in research

Every two years, the Office of Emerging Frontiers and Multidisciplinary Activities (EFMA) under the United States National Science Foundation identifies pioneering research topics for the NSF Emerging Frontiers in Research and Innovation (EFRI) program.

In 2018 and 2019, the EFRI program focused on chromatin and epigenetic engineering to uncover new ways to manipulate gene activation and deactivation.

Working under four-year grants, interdisciplinary teams tackle challenging, high-risk, high-reward projects to address some of the nation’s most pressing challenges.

Through increasing our understanding and developing innovative tools, these advancements have the potential to combat diseases, enhance crop performance, or even develop organisms that can remediate environmental damage.

Gene regulation and tissue regeneration

One team of scientists has developed a high-resolution genome imaging platform to visualize chromatin in 3D, enabling more accurate predictions for genome engineering outcomes.

This can lead to precise manipulation of genes with applications in cancer treatment, organ regeneration, injury prevention, and reversing aging.

Drugs and interventions are being developed to target cells affected by cancer or oxygen loss from strokes or heart attacks.

Understanding DNA arrangement

Another team discovered that a special protein complex called INO80 is a crucial driver of chromatin movements inside the nucleus.

Using a newly engineered device, the experts can now observe chromatin interactions happening in real time inside living cells. This can greatly contribute to the understanding of tissues made up of many different cell types, such as the brain or immune system.

Pioneering genetic delivery

Using principles derived from paper art origami, a group of researchers has made significant advances in delivering DNA into cells using nanostructures.

DNA can be packaged very tightly within these intricate designs, enabling even the longest genes to be delivered into the nucleus.

This method offers a safer, more cost-efficient alternative to traditional viral gene therapy and holds promise for treating diseases and enhancing live cell imaging.

A new path to gene regulation

Another project harnesses the power of chromatin and epigenetic engineering to combat disease.

The researchers developed new genome-editing technologies to target the non-coding regulatory regions of DNA that turn genes on or off.

These epigenetic marks can mimic changes that might occur in response to the environment – assisting in tailoring disease interventions more accurately.

New generations of scientists

EFRI teams provide valuable experiences for aspiring scientists through NSF Research Experience and Mentoring programs.

These programs offer paid research experiences and mentoring to promote diversity and inclusion within the field of gene and epigenetic engineering.

Such collaborative efforts are fuelling scientific advancement and cultivating a new generation of scientists equipped to tackle complex challenges in genetic and epigenetic engineering.

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