• Question: what has been your best scientific discovery

    Asked by dominich on 7 Jun 2019. This question was also asked by tjfinn, knjoshob, watermelon123, potatochild, benwilliamson.
    • Photo: Ettie Unwin

      Ettie Unwin answered on 7 Jun 2019:


      During my PhD I showed that you could predict how a design of something (like a bridge) would behave when it is built thousands of times quicker than had been possible before without making huge simplifications. This has the potential to change how engineers design things and help stop problems like the London millennium bridge project. This bridge had to be closed down the day it was opened because when people walked across the bridge they made it sway dangerously. With the methods I worked on, the designers could have checked this more quickly before it was built!

    • Photo: Nina Rzechorzek

      Nina Rzechorzek answered on 8 Jun 2019:


      So far, probably what I found during my PhD which focused on the molecular mechanisms of hypothermic neuroprotection (how cooling protects brain cells).

      Innovative strategies are needed to protect the brain. Cooling is robustly neuroprotective, but currently of use in just a few patients with acute brain injury (such as babies starved of oxygen at birth). My PhD was driven by the concept that greater therapeutic potential may lie in understanding how cooling protects brain cells at the molecular level. Previous studies in rats had suggested that cooling could precondition or ‘train’ the brain to cope with injuries that would otherwise be lethal. Using human brain cells grown from stem cells, I mimicked clinical cooling in the lab to explore how molecular consequences of this protected brain cells from common injurious factors.

      Cooling produced a molecular ‘cold-shock’ response in human brain cells and protected them from key death-inducing factors. It also dramatically affected tau—a brain cell protein that becomes irreversibly modified in neurodegenerative disorders, such as Alzheimer’s disease. Remarkably, cooling returned tau to a ‘foetal-like’ state, providing evidence that cooling partially reverses development in human brain cells. Moreover, by causing a mild cellular stress, cooling preconditioned the unfolded protein response (UPR)—a cellular signaling cascade that maintains protein quality control, but becomes overwhelmed in neurodegenerative diseases. I demonstrated that cold-induced changes in tau and the UPR represent significant components of hypothermic neuroprotection. Since cooling protects brain cells from molecular stressors implicated in both traumatic and degenerative processes, understanding the molecular biology of cooling (cryobiology) could reveal multiple therapeutic targets for brain disorders—without cooling patients.

      All of my work has been published in Open Access journals, which means anyone can read it online for free. Here are some of the publications relevant to this work:

      https://www.ebiomedicine.com/article/S2352-3964(15)00098-5/pdf
      https://www.ebiomedicine.com/article/S2352-3964(15)30015-3/pdf
      https://www.ebiomedicine.com/article/S2352-3964(15)30243-7/pdf

    • Photo: Thiloka Ratnaike

      Thiloka Ratnaike answered on 9 Jun 2019:


      Well, I don’t feel like I have discovered much at this point in my career apart from more questions than when I began (which is normal). However, I am proud of starting to look deeply into the question of why patients with certain mutations in their mitochondrial DNA have different diseases despite having the same mutation. I came up with a way to start to predict prognosis in patients with the same mutation in the mitochondrial DNA, during my PhD. I also looked a little into how effects of ageing in muscle at the mitochondrial level, could be reversed with a combination of resistance and endurance exercise, which was cool to see. I am currently excited about trying to attack the question around finding specific relationships between types of mitochondrial disease and the mutations causing them – this is a minefield of a topic, but I am starting to make little in roads, and the smallest of victories still count!

    • Photo: Kate Timms

      Kate Timms answered on 10 Jun 2019:


      In my PhD I discovered a new nutrient in fruit and vegetable that might make placentas grow and function better in pregnant women. Hopefully this will eventually help make sure that babies are born healthier and go on to live long, healthy lives! 😀

    • Photo: Kaitlin Wade

      Kaitlin Wade answered on 10 Jun 2019:


      My most interesting discovery was based on the most recent collaboration that I was part of. I worked with a group in Boston, America to look at whether you could use genetic information to predict whether someone was more likely to be obese at an early age. We used genetic information that we know is linked to obesity in adults and looked to see whether these same genetic markers were associated with weight and obesity in children. We found that this same genetic information was associated with obesity in children as early as 4 years old! This means that there may be a way that we could identify people who are more likely to go on to be obese in adulthood from a very early age and alter their lifestyle so that we can attempt to prevent them from become obese later in life. This was a pretty cool project to work on. You can see the paper here if you’re interested to read more (the graphic is quite good and explaining what we did): https://www.cell.com/cell/fulltext/S0092-8674(19)30290-9.

    • Photo: Rachel Hardy

      Rachel Hardy answered on 10 Jun 2019:


      So far in my PhD, I have discovered new medicines that cause damage to mitochondria in cells. This is known as an off-target effect: meaning that the drug is not intended to have an effect on mitochondria. Sometimes, this can happen with drugs due to their chemical structure (think of this as the way chemical elements that make up the drug are arranged). This structure allows the drug to bind to a target in the body (usually a protein), which treats the disease. Sometimes these structures can also bind to other proteins in the body, which are not necessary to treat the disease. This causes side-effects (as the drug stops the protein from carrying out its normal function). The drugs I am testing stop proteins in mitochondria making energy effectively. This is very damaging for organs in the body that need a lot of energy to work properly (such as the brain, liver or heart). I have also discovered which proteins the drugs bind to in the mitochondria, as well as exactly which part of the protein the drug binds. I hope to discover which part of the drug chemical structure allows it to bind to mitochondrial proteins. This may help drug discovery scientists in the future, by alerting them to drug chemical structures that may damage mitochondria. This could help lead to safer drugs being developed for patients.

    • Photo: Rebecca Moon

      Rebecca Moon answered on 10 Jun 2019:


      The main focus of my research has been on vitamin D and whether increasing a woman’s vitamin D level in pregnancy has benefits for her child, particularly in regards to the child’s bone strength and body composition. So I’ve made a few small scientific discoveries that are all part of a bigger jigsaw puzzle. For example, I’ve looked at what determines the level of vitamin D in pregnant women, and found it is related to season (higher in summer when we have more sunlight as vitamin D is primarily obtained from the action of sunlight on the skin), the use of supplements, weight gain in pregnancy, and the woman’s genetic make-up with regards to enzymes involved in vitamin D synthesis and breakdown. We all have the enzymes to make vitamin D, but the genes encoding these have small changes in them, and depending on which version of the gene you carry, your vitamin D level might be higher or lower. Although these are only small discoveries at the moment, it is likely in the future doctors will deliver a much more personalised medicine and calculate drug doses based on a patients genetics and other characteristics, so these small discoveries will potentially lead to a more personalised vitamin D dose.

    • Photo: Matthew Bareford

      Matthew Bareford answered on 11 Jun 2019:


      During my degree studies, I worked on developing possible new compounds to use for anti-cancer medication, and one of mine was put forward to clinical trials – so that was pretty cool!

    • Photo: Shobhana Nagraj

      Shobhana Nagraj answered on 11 Jun 2019:


      I haven’t really made a scientific discovery as yet – am still working on it! Working as a surgeon in Africa, I found out about some new ways in which the local doctors looked after wounds and burns – using honey and clarified butter (called ghee) and also using sterilised potato skins, and betel nut leaves for some wounds. I thought these techniques were really exciting discoveries for when there were no bandages available, and we could learn from these practices when designing new affordable materials for surgery worldwide. Currently, I work with rural healthcare workers in India to help identify women who have high-risk pregnancies using digital technology. I think that digital technologies might be used in the future to provide support and make a diagnosis without the need for a doctor, in areas of the world where there are not enough doctors, and it would be great to discover new knowledge in this area.

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