How do cells regulate the activity of specific genes?

Every spring flowering plants re-emerge in a burst of colour, but how do plants know that it’s really spring rather than just a warm spell mid-winter?

In order to not find themselves mid-bloom in January and victim to the next frost, plants must sense and remember that they have experienced a prolonged period of cold before flowering.

The influence of cold on flowering is a process called vernalization. Different plants need different lengths of cold, an adaptation to growing in different climates.

The Professor Dame Caroline Dean lab works on understanding how plants sense and remember winter.

Using a molecular genetic approach in Arabidopsis thaliana the lab has identified the genes and mechanisms behind why some plants overwinter before flowering, how plants remember cold exposure, and how flowering mechanisms have adapted to different winters.

This has led them to a focused study on a particular gene, known as the floral repressor FLOWERING LOCUS C (FLC).

As plants experience the prolonged cold of winter the floral repressor gene FLC is progressively silenced through a cis-based, Polycomb switching mechanism.

The lab are working on mechanistically dissecting what is going on in order to understand the roles of chromatin and antisense RNA regulation in this process.

Within the Dean lab, Dr Pawel Mikulski is focused on the molecular events behind what constitutes the cold-induced silencing of FLC and how that silencing is remembered through subsequent cell division ( this is called epigenetic regulation). He is looking for an answer to the question; how do cells regulate the activity of specific genes, switching them on or off in response to different cues?

“Protein machines that regulate gene expression float in the nucleus; yet they do not target the whole genome, only a subset of all the possible genes.

It was always fascinating to me how these protein machines find their targets – it seemed like a search for a needle in a haystack.

That’s especially intriguing, given that there is a relatively small number of these protein machines (hence the name ‘master regulators’) and many do not show strong DNA sequence-specific binding, so there must be more to it than just proteins binding to specific DNA sequences.

Finding out the answer is more than just scratching an academic itch because it is those scenarios where gene expression regulators get mutated and go awry that result in diseases such as cancer.

In cancer, protein machines bind wrong pieces of DNA or lose DNA binding so incorrect genes are expressed, which leads to abnormalities in cell developmental program. Mutations in master regulators in plants cause developmental defects such as improper organ formation or the presence of undifferentiated cells instead of specific tissues – it’s a complete mess.

Gene regulation is conserved across biological kingdoms. I’d like to answer the question -how do cells regulate the activity of specific genes.

I have always liked the idea of discovering something new and trying to figure out things that are not man-made and bigger than an individual. A career in biological science ticks all of those boxes.

It may surprise non-scientists but we rarely achieve a single big breakthrough and even the breakthroughs we do achieve are a composite of many smaller bricks of accrued knowledge.

In an attempt to answer this question, through my career so far, I have been able to add three main bricks to our wider wall of knowledge, showing that master regulators of gene expression are;

  1. Frequently present at the periphery of the nucleus and that they interact with some of its structural components, in-turn showing that the spatial position of the genes is important to control their expression
  2. More evolutionary conserved than previously anticipated – this means we can look at simple eukaryotes that can be easier to handle to study master regulators’ function
  3. Bind to DNA in a rather complex manner, indicating sophisticated mechanisms for fine-tuning their targeting, thus preventing their binding to the wrong DNA sequence

In terms of my future career, there are many fascinating things in the world. One needs to revisit a life-plan every couple of years, so I keep the door open. My interests used to lie in a mixture of biology and chemistry, but over time this has matured into an interest in biotechnology and molecular biology.

Initially my interest in biology arose from a mixture of sci-fi books, good teachers, support to follow my interests from my parents and the fact that I liked being outdoors.”

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