How can we improve the immune system? By watching the clock

12 May 2017

Dr Annie Curtis, research lecturer at RCSI. Image: RCSI

Dr Annie Curtis has been awarded a L’Oréal-UNESCO For Women in Science Fellowship for her work on internal clocks and the immune system. She spoke to Claire O’Connell.

Most of us wake up in the morning, eat during the day and go to sleep at night. Without even thinking about it, we are governed by our body clock – or rather, clocks, because different tissues in our bodies have their own internal clocks. 

These form a key timing mechanism within our cells to keep us in tune with circadian rhythms, or (roughly) 24-hour cycles.

“The clock is such a big modifier of all our physiology,” explained Dr Annie Curtis, a StAR (Strategic Academic Recruitment Programme) research lecturer at the Royal College of Surgeons in Ireland who has just won recognition from L’Oréal and UNESCO for her work in the field.

You have probably felt the impact of your inner clocks becoming disrupted in the form of jet lag, where the various tissues re-synchronise at different rates, leaving you feeling out of sorts.

Curtis is interested in how the running of the clock can affect our health. “I would be surprised if there is any condition out there where the clock doesn’t have an impact,” she said.

“But where it is really showing through is chronic diseases.”

Keeping time for the immune system

The signs are there if you look at immune-related conditions, Curtis noted, some of which can deal out more severe symptoms at particular times of day.

“Asthma rears its head at 4am,” said Curtis. “And rheumatoid arthritis is highly circadian – lots of people with it have more stiffness in the joints when they wake up in the morning; the clock is regulating pro-inflammatory mediators and this is dysfunctional in rheumatoid arthritis.”

Curtis looks at the clock in a type of immune cell called a macrophage, which plays a key role in triggering inflammation in the body. “There is a clock in the macrophage, and we want to know what is it doing,” she explained.

Getting to the heart of the clock

Her interest in this field was sparked when, after her BA in genetics from Trinity College Dublin (TCD), she went on to undertake her PhD in the early 2000s with Irish doctor and researcher Prof Garret FitzGerald at the University of Pennsylvania.

“At that point, there was not really a lot known about the clock, full stop,” recalled Curtis. 

She started working there on clock genes and proteins in the vascular system.

“You are much more likely to have a heart attack in the morning, and people think that is just because you are getting up, but the signature appears before you get out of bed – there is an endogenous rhythm,” she said. “We wanted to find out how clock factors are activated and drive gene transcription, and how they control blood pressure, so we worked out some of those [cellular] pathways.”

Following her PhD, Curtis went to GlaxoSmithKline in Philadelphia to work on inflammation, returning to Ireland in 2008. It wasn’t a good time to be looking for an academic post, so she worked with Science Foundation Ireland first, before moving to Bristol-Myers Squibb.

The macrophage connection

The lure of academic research was strong though, and she got her break in Ireland thanks to Prof Luke O’Neill at TCD. “I went to research in his lab and he allowed me to work on clock in macrophages, he gave me the freedom to do that,” said Curtis.

She and her colleagues teased out links between the clock in macrophages and inflammation. They found that a key microRNA involved in inflammation targets the clock protein in macrophages, and that knocking out the clock alters the immune response.

Curtis now has her own lab at the Department of Molecular and Cellular Therapeutics in RCSI, where she is continuing to explore this particular area.

“The objective is to understand what the clock is doing in the macrophage and improve clock function,” she said. “If we can improve clock function, that can lead to healthier life.”

She is also working with information from a UK biobank that has collected 24-hour information on physical activity and biological samples from around half a million people. This provides a rich source to mine for patterns about circadian rhythms.

“We are starting to figure out how lifestyle and environment and genetics impact on circadian rhythms,” said Curtis.

L’Oréal-UNESCO award

Earlier this month, Curtis was awarded a For Women In Science Fellowship from L’Oréal and UNESCO, and she attended the awards ceremony in the august surroundings of the Royal Society in London.

“The ceremony was great, it was all Dame this and Sir that,” she said. “If the Queen had dropped by, I wouldn’t have batted an eyelid.” 

The award offers her flexibility – she can use a portion of the funding for childcare, and it will also allow her to explore an interesting experiment that could form the basis of a new project – and she is now part of a global network of award recipients. “The network is a big positive,” she added.  

Night owl

While Curtis continues to delve into the molecular mechanisms that control our immune systems across day and night, she has some sound advice for fortifying our inner clocks, whether we are larks or owls.

“Keep a regular schedule, get lots of outside light during the day, and reduce your exposure to artificial light at night, especially the blue light from screens,” she said.

“And, as much as possible, get enough sleep – enough that you don’t need an alarm clock in the morning.”

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Dr Claire O’Connell is a scientist-turned-writer with a PhD in cell biology and a master’s in science communication