This week I spent two days at a local primary school as part of British Science Week 2016. For the first day I ran a mobile DNA workshop visiting all the KS2 classes (ages 7-11). We extracted DNA from strawberries. Their existing knowledge and ideas surrounding DNA was both impressive and amusing; I asked them where we keep our DNA:
“In little pots”
Such a lovely way to describe cells! They had a preformed idea of what the DNA would look like and were quite surprised that the resulting white goop didn’t quite resemble my model!
Can I have your job?
The second day I spent visiting each EYFS and KS1 (ages 4-7) class with a germ and hand-washing workshop. I also got them to design and draw their own bacteria using our collection of GIANTmicrobes as inspiration.
Q: Where do bacteria live? A: “In Australia and Poland”
My favorite part of the week was answering their questions such as “what is your most recent discovery?” and “can you make a potion that makes people invisible?”. Hopefully I managed to inspire the next generation of scientists despite revealing that in fact, no; I cannot make an invisibility potion.
A unique science communication series based on a journal article that featured in my teaching this week. The article must be open access (or freely available somewhere on the web) and broadly related to my research interests.
Scientists demonstrated over 80 years ago that calorie restriction can slow ageing and extend the lifespan of rats. This finding was later confirmed in organisms such as yeast, worms and mice; but can calorie restriction also extend human lifespan? In 2014, we almost got an answer…
According to a study first published in Science (2009) and updated in Nature Communications (2014), calorie, or caloric, restriction (CR) slows ageing in the non-human primate species, rhesus macaque. Genetically, rhesus monkeys are approximately 97.5% similar to us humans making the results of this study particularly exciting for age-related research.
Rhesus monkeys fed a calorie restricted diet not only looked younger but calorie restriction also lowered the occurrence of age-related diseases such as diabetes and cancer. Age-related survival was significantly improved under calorie restriction. In fact, animals in the control group were three times more likely to die of an age-related cause when compared to calorie restricted animals. Only 50% of control fed animals survived at the time of publishing in Science compared with 80% of those in the calorie restricted group.
Calorie restriction is a diet that reduces calorie intake without malnutrition; all essential nutrients are still provided. This 25 year long study began in 1989 at the Wisconsin National Primate Research Center, University of Wisconsin. Over 70 adult monkeys were included, the calorie restricted group’s diet was reduced by approximately 30% whilst the control group could eat to their heart’s content.
This study provides evidence that the beneficial effects of calorie restriction observed in small animal species are conserved in primates. Can we now use this knowledge to the benefit of humans? Many believe the existing scientific evidence is enough, especially given that anecdotal evidence dates back hundreds of years. Take for example Francis Bacon (1561–1626) who stated: ‘‘it seems to be approved by experience, that a spare diet…rendereth a man long-lived’’. It is no surprise then that in today’s diet obsessed world calorie restriction already has a dedicated following, complete with its own society. How do you fancy it? I certainly couldn’t tolerate the 30% reduction in calorie intake imposed on these monkeys, but one possibility, already under intense investigation, is the development of drugs that mimic the mechanisms activated by calorie restriction – so called calorie restriction mimetics (CRMs).
Candidate CRM compounds include resveratrol and rapamycin, both of which are no strangers to media reports. ‘Fountain of youth’ pills containing some form of resveratrol and rapamycin are even available in commercial supplements.
Resveratrol is a naturally occurring compound found in red grapes, it is thought to target a group of proteins called sirtuins that regulate metabolism. Some evidence suggests that both calorie restriction and resveratrol extend lifespan through the activation of these sirtuin proteins.
Rapamycin decreases the activity of a protein called mTOR that, in response to nutrients, has several important functions in cell growth and survival. This decrease in mTOR activity is also observed under a calorie restricted diet.
I would not get too excited. It is unlikely that a single drug could mimic the full biological effects of calorie restriction, and what of the side effects? Following a calorie restricted diet is not without both physical and psychological risk. Tissue loss, reproductive issues, slower growth and wound healing, hunger, obsession and mood changes are just a few of the disadvantages. Whilst human studies are underway, the long-term effects of following a calorie restricted diet or popping CRM pills are unknown.
Advocates of calorie restriction propose that the life extending mechanism is evolutionary conserved, but the field has become heavily contested. Some evidence suggests that the beneficial effects of calorie restriction are not universal, for example there are differences in response between different strains of mice. Our genetic make-up could therefore prove to be a more important factor in determining lifespan than diet and lifestyle.
Another reason to remain cautious comes from a conflicting rhesus monkey study from the National Institute on Ageing (NIA) that failed to find a significant difference in lifespan between control and calorie restricted monkeys. The discrepancy could be explained by differences in experimental design (e.g. diet regimen and composition) and the control group’s diet has been the focus of much scrutiny. An ad libitum diet, as used in the Wisconsin study can result in over feeding, weight gain and early onset disease. In some ways, this does mirror the modern human diet but also arguably heightens the effect of calorie restriction. On the other hand, the control animals in the NIA study were fed a portioned diet resulting in lower than average body weights. These animals may well have been mildly calorie restricted and clouded the results. A thorough analysis and comparison of the data from both studies will be well under way by now to determine the true extent of lifespan expansion in calorie restricted monkeys.
I will not be joining the calorie restriction society. I am more intrigued by the search than the actual ‘fountain of youth’; searching for it could unravel biological mechanisms of ageing and longevity and provide a more immediate benefit for human health.
This past week I have spent a lot of time on PubMed. So today I’m following up from a previous post on teaching students and early career researchers more efficient strategies to search and retrieve medical/life science literature. This post will focus on a couple of overlooked tools within PubMed. Let’s start with an overview of my PubMed search strategy*, click through the presentation below:
This tool quickly filters your search to only the clinical literature and groups results into three different categories (clinical study, systematic reviews and medical genetics) all displayed on the same page. The medical genetics column is especially useful in finding variations associated with a disease. You can further target your search by selecting either etiology, diagnosis, therapy, prognosis or clinical prediction guide under ‘category’.
Using a combination of complimentary search strategies will maximise retrieval. Always perform a standard text/key word search but then try an alternative method (including other databases such as Google Scholar that work quite differently), these will give you different top hits and articles you would have missed when solely relying on on a single search strategy.
*Note that before you do this you will need to have developed a good research question. Break this down into concepts to help you identify starting keywords.
Now feels a good time to start an academic parenthood category on Weekademia. I have a toddler, two cats and a husband and am a lecturer in a post-1992 institution that is finally beginning to buzz about Athena SWAN.
“Work-life balance doesn’t exist for me; I don’t believe in unicorns”
I share this viewpoint that my work is a part of my life in which I also happen to be a mother and Lady Dr of the household. I’m not attempting to combine work and family, I am combining work and family. It is hard at times and I really should accept that I need to hire a cleaner but it is what it is and you just get on with it.
My story? Baby Weekademia was born towards the end of what turned out to be my last post-doc, five years post PhD. I wangled a whole year of maternity leave (maybe it’s easier for a post-doc?) – although, as my project continued whilst I was away*, I only had four months of funding left when I returned. I was OK with this seen as we had made the decision to relocate at that point anyway (who says you can’t go home?). Knowing this, I felt I had to use my leave wisely: I put my CV in order and finished writing my HEA application for associate fellow. For me, those first four months of being a working mother were make or break. It wasn’t all rosy managing without any family nearby, but it turned out baby Weekademia thrived in nursery and I was enjoying being back at work. It wasn’t long before I found myself a stay at home mom for the summer whilst we relocated, this was great but the stress of finding a place to live and a new job made it difficult to make the most of it.
Now all settled into a new home, nursery and job, I keep getting asked how I manage a 50 minute commute between nursery and work. I share drop-offs and pick-ups with my husband of course, but the commute doesn’t bother me. I have always had ~an hour’s commute and the drive home provides time to shut down and digest the day. I put back on my mommy hat as I drive across the Northamptonshire/Warwickshire border (although I don’t think I need one with the constant smears of toothpaste and snot on my shoulder!).
Let’s not pretend academics work 9-5, outside of working hours and when needs must my rule is: children above work and work above tiredness. It took me a while to be able to ‘down-tools’ at 5pm particularly as a post-doc where I was used to working working 8-8 in the lab. I felt guilty leaving baby and then guilty leaving work. I have become much more efficient and focused between 9-5 and have accepted a more agile and flexible way of working that thankfully suits academia.
For now, my life as an academic mother is, contrary to popular belief, quite manageable. Yes it is a challenge: my husband and I learned the hard way this week the importance of synchronised diaries – which reminds me I need to schedule the nursery Christmas extravaganza (roles to be announced soon…what!? is baby going to need some sort of costume?).
Parent or not, all this talk of work-life balance in academia makes you feel depressed and inadequate and I wanted to share my relatively positive experiences…although baby has yet to reach school age which I think will pose the biggest challenge…What are your stories and advice for academic parents?
*There’s a dark side to maternity leave you rarely hear about – the feelings and awkwardness associated with having someone else replace you and carry on your work. They may be better than you, or completely ruin the project – what about authorship and presenting at conferences etc? I have experienced this both as an employed maternity cover myself and as ‘the new mother’; it can cause quite a bit of stress for both parties.
“It is bad academic practice to limit your search to only literature that is open access.”
A key area of frustration for undergraduate life science students in smaller and/or less research intense universities is the difficulties associated with accessing full text restricted access journal articles on the web. It is challenging enough to perform a systematic literature review in the first place and despite the joys of finding a most brilliantly relevant article, students are giving up at the first ‘access denied’ stop sign; they are left hanging on inter-library loans and feeling dissatisfied with library services.
This stems in part from a lack of understanding of the publication process and open access policies etc. and from not knowing how to utilise the resources they already have available at their fingertips (do they know they exist at all?) which, in many cases, can bypass access restriction. Librarians are fantastic and worth their weight in gold, but when librarians are not close enough to your discipline should we be supplementing their service with specialised tutorials from research-active staff themselves? Moving towards a more research orientated education, teaching students the tricks of the trade often not picked up until postgraduate study may help to produce more resourceful and proactive students who could have a competitive edge in the job market.
As part of a programme wide response to issues raised by our students I am preparing a series of vlogs to demonstrate in real time how I do my own literature searches and how I go about accessing restricted access articles. I certainly do not claim to know the ins and outs of every tool and database out there and there may be better methods but I think imparting my researcher’s knowledge on the students now will mean they’ll have a firmer base on which to seek more advanced training from librarians on only the most relevant of resources.
I’m a month into this new position, so an exercise like this is going to help me as much as the students in learning the full extent of the access restrictions the students are facing here. From watching me navigate a new university library system the students will see for themselves how far a little bit of resourcefulness and proactivity can take you. I’ll let you know how it goes, and possibly update this post with links to the material…
This week we are welcoming new students to the university (perhaps the subject of next week’s blog…) but over the last couple of weeks I’ve been experiencing my very own welcome as a new member of staff.
I’m excited to see how Weekademia will grow and evolve here at Northampton, especially as I begin to develop and use blogging as a teaching tool for the life sciences. For now, I’ll point you towards the ‘Academic musings from the University of Northampton’ blog where I’ve written an opinion piece on the development of a blood test that can reveal how well you are aging and predict longevity.
Today is the second World Duchenne Awareness Day, the 7th of September 2015. The 7th of the 9th. 79. This is a significant number…
These 79 boxes represent the 79 exons of the DMD gene. This gene encodes for a protein called dystrophin; do you notice that some exons are joined together like a jigsaw? As a general rule, mutations that disrupt this ‘jigsaw’ will cause Duchenne muscular dystrophy. For example, with a deletion of exon 50, exons 49 and 51 cannot slot back together and a functional dystrophin protein will not be produced. Dystrophin is very important for the normal functioning of our muscles and is virtually absent in muscle from patients with Duchenne muscular dystrophy. How does this affect muscle function and the lives of those living with Duchenne? Please start by watching and sharing this amazing video ‘Introduction to Duchenne muscular dystrophy’:
The aim of World Duchenne Awareness Day is to improve the education and awareness of Duchenne muscular dystrophy around the globe. With increased awareness comes an increased interest in the research being carried out to not only better understand and treat the disease but to also improve wellbeing, standard of care and support. The thing I love about the video is that it ends on a positive note, through research we have already begun to change the natural history of Duchenne to help provide a ‘normal independent future’ and enable these boys to ‘play a full part in society’. There is still a long way to go.
My research is predominantly focused on developing antisense oligonucleotide-mediated exon skipping as a way to piece back together that ‘molecular jigsaw’ in affected individuals. It has been a bumpy road but the FDA has very recently accepted a new drug application for the exon skipping drug, eteplirsen, and given it priority review status meaning a decision can be made as early as February 2016. However, this drug can only treat patients with particular mutations and we must continue to build on our experience to help expedite the drug development pathway for other exon skipping drug candidates, including the ‘next generation’ of drugs with improved targeting and delivery.
The video also hits home that Duchenne boys are all individual. From a biological perspective the fact remains that one of the most complicating factors for developing a treatment for Duchenne is the inherent clinical and biochemical variability between patients, even between patients with the same genetic mutation. This makes the selection and validation of outcome measures for clinical trials very difficult. Overcoming these challenges is a large part of our focus in the Duchenne research community for which teams across the globe are joining forces to avoid unnecessary delays in translating this research to the clinic (see http://exonskipping.eu/ and http://weekademia.com/2015/04/13/academia-industry-relationship/).
For more information be sure to visit the World Duchenne Awareness Day 2015 website where you can also find patient photo blogs and release a virtual balloon!