Today we chat to SCI member Luca Steel about her life as a plant pathology PhD student in 2020.
Zymoseptoria tritici is a fungal pathogen of wheat which can cause yield losses of up to 50%. We’re investigating an effector protein secreted by Z. tritici which acts as a ‘mask’, hiding the pathogen from host immune receptors and avoiding immune response.
What does a day in the life of a plant pathology PhD Student look like?
My days are very varied – from sowing wheat seeds to swabbing pathogenic spores onto their leaves, imaging symptoms, discussing results with my supervisor and lab team, and of course lots of reading. It doesn’t always go to plan - I recently attempted to make some wheat leaf broth, which involved lots of messy blending and ended up turning into a swampy mess in the autoclave!
Wheat in the incubator!
How did your education prepare you for this experience?
The most valuable preparation was my placement year at GSK and my final year project at university. Being in the lab and having my own project to work on made me confident that I wanted to do a PhD – even if it was a totally different research area (I studied epigenetics/immunoinflammation at GSK!).
What are some of the highlights so far?
My highlight was probably attending the European Conference on Fungal Genetics in Rome earlier this year. It was great to hear about so much exciting work going on – and it was an added bonus that we got to explore Rome. I’ve also loved getting to know my colleagues and being able to do science every day.
What is one of the biggest challenges faced in a PhD?
My biggest challenge so far has probably been working from home during lockdown. Although I am very privileged to have a distraction-free space and good internet connection, it was difficult to adjust to working from my kitchen! It was sad abandoning unfinished experiments, and I missed being in the lab – so I’m glad to be back now.
What advice would you give to someone considering a PhD?
If you’re sure you want to do one, then absolutely go for it and don’t be afraid to sell yourself! If not, I’d recommend spending some time working in a lab before you apply and chatting to any prospective labs. If you don’t get a reply from the PI, existing students/post-docs in the group are often very happy to talk and give honest opinions.
How have things been different for you because of the global pandemic?
I was lucky that the pandemic came early on in my PhD, so I had a lot of flexibility to change what I was working on. I switched from lab work involving lots of bioimaging, towards a more bioinformatic approach. My poor laptop will be glad when I’m back to using my computer at work!
Roughly 60% of the 12 million animal experiments in Europe each year involve mice. But despite their undoubted usefulness, mice haven’t been much help in getting successful drugs into patients with brain conditions such as autism, schizophrenia or Alzheimer’s disease. So too have researchers grown 2D human brain cells in a dish. However, human brain tissue comprises many cell types in complex 3D arrangements, necessary for true cell identity and function to emerge.
Researchers are hopeful that lab grown mini-brains – tiny 3D tissues resembling the early human brain – may offer a more promising approach. ‘We first published on them in 2013, but the number of brain organoid papers has since skyrocketed, with 300 just last year,’ says Madeline Lancaster at the Medical Research Council’s Laboratory of Molecular Biology lab in Cambridge, UK.
Lancaster was the first to grow mini-brains – or brain organoids – as a postdoc in the lab of Juergen Knoblich at the Institute of Molecular Biotechnology in Vienna, Austria. The miniature brains comprised parts of the cortex, hippocampus and even retinas, resembling a jumbled-up brain of a human foetus.
‘We were stunned by how similar the events in the organoids were to what happens in a human embryo,’ says Knoblich. To be clear, the brain tissue is not a downsized replicate. Lancaster compares the blobs of tissue to an aircraft disassembled and put back together, with the engine, cockpit and wings in the wrong place.
Growing mini brains to discover what makes us human | Madeline Lancaster. Video: TEDx Talks
‘The plane wouldn’t fly, but you can study each of those components and learn about them. This is the same with brain organoids. They develop features similar to the human brain,’ she explains.
In early September of this year, 34 final year chemists from all over the United Kingdom descended on GSK Stevenage for a week of all things chemistry, at the 14th Residential Chemistry Training Experience.
A few months prior, an e-flyer had circulated around the Chemistry department at UCL. It advertised the week-long, fully-funded initiative created to give soon-to-be grad chemists insight into the inner workings of the pharma industry. We were told we would also receive help with our soft skills – there was mention of interview prep and help with presentation skills. As someone who doesn’t have an industrial placement year structured into their degree, I was excited to see how different chemistry in academia might be to that in industry, or if there were any differences at all.
A fraction of GSK’s consumer healthcare products. Image: GSK
Two days in labs exposed me to new analytical techniques and gave me an appreciation for how smoothly everything can run. I was assigned a PhD student who supervised me one-on-one – something you’re seldom afforded at university until your masters year. We hoped to synthesise a compound he needed as proof of concept, and we did!
The abundance in resources available and state-of-the-art equipment at every turn highlighted how different an academic PhD might be to an industry one if that’s the route I decided to go down. The week bridged the disconnect I had between what I’d learnt at university and how things are done or appear.
The GSK training course gave me unique insight into the life of a working scientist. Image: Pixabay
For example, I know enzymes can be used to speed up the rate of a biological reaction, but I’d never stopped to think about what they even look like. They come in the form of a sand-like material, if you’re wondering. Before that week, I hadn’t seen a Nuclear Magnetic Resonance (NMR) machine – we’d hand in our samples and someone else did the rest. NMR is an analytical technique we employ to characterise samples, double-checking to see we’ve made the right thing. It was great to put all this chemistry into context.
Our evenings were filled with opportunities to meet GSK staff and a networking formal brought in many others from places like SCI and the Royal Society of Chemistry.
A Nuclear Magnetic Resonance (NMR) machine, used by scientists to determine the properties of a molecule. Image: GSK
During the week, there was a real emphasis on equipping us with the skills and confidence to succeed in whatever we opted to do. That’s exactly how I felt during our day of interview prep. The morning started off with a presentation on the structure of a typical graduate chemistry interview, followed by a comical mock interview before we were set loose with our own interviewer for an hour. Before this, I’d never had someone peer over my shoulder as I drew out mechanisms, and I’d never anticipated that I’d forget some really basic stuff.
The hour whizzed by and when I was asked how I thought it had gone – terribly – and I was met with feedback that not only left me with more confidence in my own abilities, but an understanding of what a good interview is. It’s definitely OK to forget things – we’re human – but what’s most important is showing how you can get back to the right place using logic when you do forget.
Whether you’re curious about what goes on in companies like GSK, know you definitely want to work in pharma or you’re approaching your final year and just don’t know what you want to do (me), I’d recommend seeking out opportunities like this one. I got to meet people at my own university that I’d never spoken to and had great fun surrounded by others with the same love for organic chemistry.
What is paralysis? Video: Doctors’ Circle
Patients suffering from paralysis can at last look forward to a time when their condition is cured, and they can walk, run or move their damaged limbs again, as recent advancements show the possibility of reversal.
‘The environment has never been better for exploring ways to restore neurological function, including paralysis – in fact, there has been a dramatic escalation of the entire research spectrum aimed at functional neurorestoration,’ says Charles Liu, Director of the University of Southern California Neurorestoration Center.
Paralysis comes in many forms: the paralysis of one limb (monoplegia), one side of the body (hemiplegia), below the waist (paraplegia), and all four limbs below the neck (tetraplegia, or also referred to as quadriplegia).
There are many classifications of paralysis. It can be localised or generalised, and can affect most areas of the body. Image: Pixabay
In an able-bodied person, the brain sends a signal as an electrical impulse, known as an action potential, down the spinal cord to the peripheral nerves, which instruct the muscles to contract and move, whereupon sensors in the muscles and skin send signals back to the brain.
In most paralysis cases, the condition occurs as a result of damage to nerves rather than an injury to the affected area. Strokes are the most common cause of paralysis, followed by spinal cord injuries. Multiple sclerosis, cerebral palsy, polio, head injuries and several other rare diseases can also cause paralysis.
‘Long term, we hope to cure paralysis and make the injured walk,’ explains William Sikkema, a graduate student at Rice University, Houston. The challenge is not only to repair cells but to restore connectivity, too. In collaboration with researchers at Konkuk University in South Korea, the team has already made a paralysed rat walk again.
The addition of graphene nanoribbons restored motor and sensory neuronal signals across the previous nerve gap after 24 hours, with almost perfect motor control recovery after a period of healing. ‘Two weeks later, the rat could walk without losing balance, stand up on his hind limbs and use his forelimbs to feed himself with pellets. No recovery was observed in controls,’ the team reported.
‘After a neuron is cut, it doesn’t know where to grow. So, it either doesn’t grow, or grows in the wrong direction,’ says Sikkema. ‘Our graphene nanoribbons act as a scaffolding track, and it tells the neurons where to grow.’
Rats are a common animal model in paralysis studies, as they share similar structure and functions with humans. Image: Pexels
Spinal cord stimulation
Electrical stimulation of the spinal cord could also provide a big breakthrough, says Chet Moritz, Co-Director of the Center for Sensorimotor Neural Engineering at the University of Washington, US.
‘We’re seeing some really impressive results with spinal cord stimulation where people with complete paralysis, who have been unable to function, have regained control of their limbs. We didn’t expect this. It’s the most exciting thing we’ve seen in the last 20 years,’ he says.
Last year, a team led by Grégoire Courtine at the Swiss Federal Institute of Technology inserted an implant in the brains of paralysed monkeys and another over the spinal cord below the injury. The brain-spine interface worked by capturing leg-moving brain signals, decoded by a computer and sent – bypassing the damaged region – to the second implant, which delivered the signals as electrical impulses to the nerves, causing the leg to move.
Grégoire Courtine talks about his pioneering work on paralysis using electrical stimulation. Video: TED
Within six days, the monkeys had regained the use of their lower limbs and improved even more over time. The success of the experiment has led Courtine to launch a human trial of a spinal implant system.
We may be a long way still from restoring full function, as prior to paralysis, but Moritz is optimistic. Even a modest change, such as the movement of a single finger, can have a dramatic effect on quality of life and independence. ‘In five years, we’ve had dramatic improvement in function,’ he says. ‘It’s an exciting trajectory with tremendous potential.’