Profile: Qing-Jun Meng
Qing-Jun Meng is an MRC fellow at the University of Manchester. He told Katherine Nightingale about his research into biological clocks, their role in age-associated conditions, and how they offer a whole new way of looking at disease.
How does a Chinese flight surgeon end up researching biological clocks in Manchester? In the early 2000s, Qing-Jun Meng was advising pilots and medical officers for astronauts in China’s burgeoning space programme. Now he’s halfway through an MRC fellowship researching how changes in the body’s circadian rhythm during ageing cause disease.
The two fields aren’t actually so different, says Qing-Jun. “It sounds like discipline hopping but some of the lectures I gave to pilots were about body clocks and jet lag. That was when I first got interested in the field.”
Frustrated by the lack of opportunity to do cutting edge research, particularly that which would benefit people, Qing-Jun began applying for postdoc jobs abroad. His acceptance to work in vascular tissue engineering at Manchester Royal Infirmary was the first step; a second step just down the road to the University of Manchester landed him in biological clocks, where he’s remained ever since.
Anyone who’s ever experienced jet-lag will be aware that humans have an internal biological ‘clock’, or circadian rhythm. This body clock runs on a near-24-hour cycle. Part of the brain’s hypothalamus detects light and in turn determines whether particular genes, called clock genes, are activated or deactivated depending on the time of day. As the levels of the proteins that these clock genes make rise and fall, they control biological processes such as sleep and metabolism.
As well as this ‘master clock’, most organs and cell types have their own clocks, known as peripheral clocks, which are synchronised to the master clock. These peripheral clocks keep biological processes in the organs to a daily rhythm. For example, under the control of the master clock, the pineal gland secrets a hormone called melatonin (known as the ’hormone of darkness’) exclusively during the night.
Mutations in clock genes can cause sleep disorders where a person’s night’s sleep is shifted either much earlier or much later in the day. But clock genes play a role in other diseases too, and that’s where Qing-Jun’s research comes in.
Qing-Jun is interested in how peripheral clocks are affected by the ‘dampening’ of the master clock with age. Levels of melatonin in the blood, which can be used as a marker of circadian rhythm, are lower in older people and the hormone is released slightly earlier in the day.
One peripheral clock that Qing-Jun is looking at is that of the cartilage, a flexible connective tissue found in bone joints. He and his team have compared cartilage from young and old mice and found that the circadian rhythm in the older cartilage is dampened. Qing-Jun thinks this might be a contributing factor in osteoarthritis, a common age-associated joint disease where the cartilage at bone joints is lost.
He thinks that clock-controlled genes that are involved in synthesising new, or destroying old, cartilage can’t reach the levels they need to at particular times of the day, or can’t dip low enough at others, meaning more cartilage is lost than made.
“We don’t know yet, but we think the timing of biosynthesis/degradation of cartilage needs to be matched with daily activity, and when it isn’t, this leads to damage.”
They are now looking at specific clock-controlled genes in cartilage to see if the clock regulation of cartilage genes could be new drug targets for joint diseases.
A new angle on disease
Another area that Qing-Jun is investigating is breast cancer. Shift workers appear to be at a higher risk of breast cancer and Qing-Jun is using mice to understand why.
He’s found that a peripheral clock is at work in type of cell called mammary epithelial cells and that it controls a number of genes associated with cancer.
He’s just been awarded an MRC Centenary Award to engineer mice where the mammary epithelial cells have no circadian rhythm and see whether this could contribute to the increased breast cancer risk.
While Qing-Jun is only able to focus on a few diseases, he thinks that studying circadian rhythm and clock genes could be a whole new way of looking at and ultimately treating disease.
“In any given tissue there are many genes that are controlled by the clock, and these genes play so many different roles. Links have been found to diabetes, to obesity, to heart disease, to mental illness, to cancer.”
Strength in numbers
Qing-Jun is halfway through his fellowship and is happy with the disease-oriented direction in which his research is heading. The fellowship also meant he could set up his own lab and pursue multiple projects.
“I’m fortunate in that I can explore different areas and can then focus on a few important ones for future research,” he says.
Qing-Jun certainly has a diverse range of studies in his back catalogue, the key to which he says is collaboration. From investigating circadian rhythm in reindeer to studying the impact that lithium salt for bipolar disorder has on body clocks, almost every one of his projects is collaborative.
“I’m a big believer of collaborative research: that’s where the strength lies. You can take advantage of what each partner has and that’s really, really important for research.”