AsianScientist (Apr. 27, 2016) – In most animal cells, there are tiny structures called mitochondria, often called the powerhouse of the cell. They convert the food we eat into the energy needed for a cell to run, and are thus part of the very fabric of life.
But what about the fabric of a quilt? Sit Kim Ping, professor of biochemistry at the National University of Singapore (NUS), weaves mitochondria into the quilts she makes in her spare time.
The petite, dapper 75-year-old spreads out one of these elaborate quilts, as long as she is tall, on a couch at the home she shares with her clinician husband.
“It took me three years to make this. Here, you can see the date, 2008,” she says.
The intricate fabric—patterned with squares, hexagons and triangles—bears words such as “mitochondria” and “ATP”, a molecule that ferries energy around cells.
Professor Sit has applied the same dedication to her 50-year career, which has been spent studying metabolism—the cellular interactions that make life possible. With more than a hundred international publications, she has, among other things, shed light on human brain and liver functions, as well as the workings of cancer cells.
The fifth of nine children born to a successful restaurateur and his wife, Professor Sit grew up in Katong in the postwar years. At Tanjong Katong Girls’ School, she developed a love for mathematics and science. Later, at the University of Singapore, she chose to study science and topped her cohort with first-class honours.
“Medicine was a long course, five years, and very structured. I decided to do science, as it was only three years long, but at the end of the day, with postgraduate studies, I graduated later than my schoolmates,” she laughs.
In 1965, she went to Canada’s McGill University on a Commonwealth scholarship for graduate studies in biochemistry.
“In those days, if you wanted to study the body at that level, it was all biochemistry,” she says. “There was hardly anything about cell or molecular biology; those came much later.”
Amidst the chill and dark of the Canadian winters, where graduate students often laboured till the wee hours of the morning and slept in the department’s sick-bay, something clicked for Professor Sit.
The specifics of the experiment are lost to time, but she says, “I was doing thin-layer chromatography [a type of separation technique] and suddenly I saw something and said, hey, that’s interesting… You see something that you didn’t expect, and you have to figure it out.”
But such little “perks” of research are few and far between, she admits, “because most experiments don’t work.”
Soon, she became interested in metabolic processes. She carried out experiments in which she fed or injected different substances into rats, and then analysed their metabolic products.
“There was lots of testing of rat urine,” she says. “You put the rat in a cage with wire netting at the bottom, and collect the urine.”
In particular, Professor Sit was fascinated by a biological process called detoxification (much different from today’s faddish “detox” diets, which have no scientific grounding). Things that enter the body, such as foods we eat or drugs we take, get metabolised for use by the body, and they or their metabolic by-products must be excreted somehow.
To be excreted, those by-products must be made water-soluble by having a small molecule produced by our cells such as a sulphate attached to them, in a process called conjugation. Only then can they be passed out in urine or bile. The liver is the main organ that performs this function, but the kidneys and brain do too.
The incredible mitochondrion
Early on, Professor Sit’s research centred around understanding the mechanisms by which this conjugation process occurs. For instance, she examined how various substances are conjugated and excreted in rats—not only within the liver, but in other tissues and organs in the body. Where do conjugation reactions occur? How do different drugs or their by-products, for example, get removed from the body and how long does this take?
Even the brain, she found, is able to carry out these conjugation reactions.
“Nobody expected that,” she says. “Up to now, I’m still thinking about these possibilities, particularly in relation to children with autism.”
One research hypothesis she had hoped to test is whether autism is related to a disorder where either some brain neurotransmitters are not conjugated properly and thus cannot be excreted; or some other molecule in the brain gets conjugated instead of the target neurotransmitters. Unfortunately, she retired before she could explore this idea further.
Meanwhile, she was also fascinated by another research question that involved cancer cells and the mitochondria within them.
About 80 years ago, Otto Warburg, the German biologist and Nobel laureate, observed that cancer cells produce energy by a process called glycolysis, which does not involve oxygen, rather than by ordinary mitochondrial (aerobic) respiration, which does. He hypothesised that mitochondrial respiration was impaired in cancer cells.
“With oxygen, you get 32 molecules of ATP with every molecule of glucose [that is broken down]. But anaerobically, you only get two molecules of ATP,” Professor Sit explains.
What baffled scientists: why would cancer cells use a respiratory process that produces fewer ATP molecules with which to ferry energy around the cell? And, with fewer ATP molecules than cells that respire aerobically, where do cancer cells get the energy to grow?
However, on further investigation, Professor Sit and her colleagues found mitochondria still working and respiring aerobically in cancer-tissue samples, which ran counter to “the Warburg hypothesis”. They published their data on ovarian cancer in 2011 and renal cancer in 2015.
Professor Sit says that for years, the mitochondrion has been her favourite organelle (a specialised subunit within a cell, with its own specific function).
“In metabolic pathways, without the mitochondria, nothing would work,” she says.
So for instance, while processes inside the cell— in the liver or, say, the brain—make metabolic by-products water-soluble, it is mitochondria that generate the energy to pump them out of the cell.
Biochemistry in Singapore
Over tea, fruit, and a ginger and pear cake, Professor Sit reminisces about improvised lab equipment in the 1970s, such as one made by a colleague: it was a cooking pot with a stand drilled with holes to accommodate multiple test tubes for boiling over a Bunsen burner.
“When you’re desperate enough, you innovate,” she says. “When I moved out of my lab the research assistant said, ‘Prof Sit, what is this? It looks like a power drill.’ These days we have lots of ready-made equipment, so we didn’t need the drill anymore and they didn’t know what it was.”
It turned out that a pestle, which replaces a rotating drill bit, was used to homogenise rat livers at high speed.
Early in Professor Sit’s career, biochemistry was regarded as an illustrious discipline. But as molecular and cell biology techniques improved in the last two decades, biochemistry became “like an antique”.
But it is making a comeback, she says: “Once you’ve done the cell biology manipulation, you still need the biochemistry techniques to prove what has happened to its metabolism.”
In 2001, Singapore began its push to develop and commercialise the biomedical sciences. At the time, six departments including biochemistry, microbiology, physiology and others taught 90 or so life sciences modules “with considerable duplication”. Professor Sit chaired the working committee that integrated and streamlined the modules and implemented its new life sciences curriculum the following year.
From 2007 to 2014, Professor Sit also served as a research integrity officer at NUS, one of five faculty members appointed to look into reports of potential falsification or plagiarism.
“The pressure is to publish big—and quick,” she admits. “So these cases are everywhere, not just here [Singapore].”
The most common issue, Professor Sit says, is possible self-plagiarism, in which a researcher duplicates his or her own previously-published work in another journal without proper citation of the earlier paper.
Asked if there was anything she would have done differently in her career, Professor Sit says, “My only regret is that I did not collaborate with others that much, although I did collaborate and publish with a few clinicians in recent years on tumour biology.”
Today, producing a high-impact publication often takes a larger group of people to address a research question from different angles.
“Nowadays, you don’t see any publications with a solo author, and sometimes there are 25 authors or more in one paper,” she says.
Since her retirement in 2015, Professor Sit has had more time to spend on her hobbies: crafting and quilting. She sews her own cheongsams, collects fabric swatches from her travels, and knits.
“I’ve quilted for 30 years,” she says. “And every Saturday when I was a little girl, I used to go to the Singer [sewing-machine supply] shop to do machine embroidery, and I still have some beautiful pieces.”
Although Professor Sit lives far from her daughter and son—a paediatrician in London and a research engineer in Los Angeles, respectively—she makes it a point to have tea every Sunday with her 102-year-old mother and siblings, most of whom are based in Singapore. She shows off a family quilt: a patchwork of fabric tea cups, saucers, plates and cakes, each block picked out and sewn by a family member.
Quite fittingly, the woman who studied the powerhouse of the cell has no shortage of energy herself.
This feature is part of a series of 25 profiles, first published as Singapore’s Scientific Pioneers. Click here to read the rest of the articles in this series.
Copyright: Asian Scientist Magazine; Photo: Cyril Ng.
Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.