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Lucy’s Legs: The software showing us how our ancestors walked

Based on a presentation by Dr Karl Bates (UoL Institute of Ageing and Chronic Disease):
“Biomechanics – understanding the relationship between anatomy and function”

Happy Sunday, everyone! Hope you’re having a good weekend! Here we have a description of the 2nd piece of research presented at the evening of seminars I attended last week. Enjoy!

Now, the first thing you might be wondering after reading the title is, what exactly is the field of Biomechanics? I’ll admit that I’d never heard of it before this talk! Essentially, it’s the study of an organism’s moving parts in order to understand how their arrangement relates to their function. Dr Bates’ research group is looking at human legs, studying the relationship between their morphology (i.e. the shape and arrangement of muscles, bones and tendons etc) and the way humans walk.

The group wants to find the muscle activation pattern that produces the fastest, or most energy-efficient, way of running. They’re carrying out their work using a technology called ‘Evolutionary Robotics’. This involves a computer program that uses a mathematical model (code for ‘maths 99% of us can’t hope to grasp’!) with values for every single muscle in the pair of legs.

An example of a Gait Lab - this one is at Strathclyde University. The test subject walks/runs between the cameras with sensors attached to their legs so that a computer can recreate the motions they pick up. This is similar to the technology used to create film characters like Gollum in The Lord of the Rings.

An example of a Gait Lab – this one is at Strathclyde University. The test subject walks/runs between the cameras with sensors attached to their legs so that a computer can recreate the motions they pick up. This is similar to the technology used to create CGI film characters like Gollum in The Lord of the Rings. (Photo Credit: Strathclyde University)

The system takes recordings of a human running through the group’s ‘gait lab’ and matches the pattern of muscle activation it sees.  It then tests every possible combination of muscle contraction strengths and timings as it attempts to create the most energy-efficient version of the running motion it saw.

Sounds relatively straightforward – leave your computer running for a while and let it come back with a neat and tidy result, right? Well….no. There are millions and millions of possible combinations that the computer needs to work through. As such, they need one impressively powerful computer, and it still takes ages!

Brilliantly, the program builds a pair of virtual human legs, including tissues, joints and tendons, so you can see how its current optimum equation works. At this point, Dr Bates showed us a ridiculous video of a pattern the computer suggested early on. The legs rotated round the hips in 360° turns, moving along like some kind of grotesque ball! One of the latest suggestions shows the legs moving normally for a while…before falling over! But it is getting there…

Now, this is all well and good, but what’s the point? Well, once the computer program has mastered the leg movement, the group can use it to understand the changes humans undergo as we age. We know that we lose muscle mass and gain fat, meaning that our bodies can’t operate in exactly the same way as when we were young. But what we don’t know is in what ways our bodies have to compensate for these changes.

Dr Bates said that, once they know how the legs move and which muscles are needed, they can start playing around with the anatomy in a way they couldn’t do in real life. They can, for example, change tendon lengths and muscle masses in a virtual pair of legs to reflect an older person’s physiology. This will allow them to see how energy efficiency changes during a person’s life-time and how different parts of the legs must change to cope with, for example, reduced muscle mass. This will give us a greater understanding of the pressures our bodies come under as they age.

« Lucy » skeleton (AL 288-1) Australopithecus ...

Casts of Lucy’s fossilised remains. These bones were all the team had to work with! (Photo Credit: Wikipedia)

Model of the australopithecus Lucy in the muse...

A very happy-looking model of what we think Lucy looked like, at the Museum of Barcelona (Photo Credit: Wikipedia)

The group’s work will also help us understand more about how we have evolved as a species. A really interesting application of the group’s work so far has been to solve the controversy over how one of our ancient ancestors – Australopithecus afarensis – walked. The best-known fossil of the species is a partial skeleton, which has been named Lucy!

Lucy is 3.2 million years young and, despite how little of her was found, researchers have estimated that the lengths of Lucy’s humerus and femur leg bones are right in-between the lengths seen in humans and chimps. So, the question is, did she walk upright like humans or using her arms like chimps?

The group used their computer program to simulate Lucy walking in both ways. They worked out that it was far more energy-efficient for her to walk upright, given her bone structure. As animals very often adapt to be more energy-efficient, it seems likely that Lucy and her Australopithecus afarensis brethren walked upright like us.

To confirm this, the group compared the heel pressure Lucy was predicted to exert when walking upright with the pressure her preserved footprint implied. The two pieces of evidence matched. So, thanks to this research and the group’s remarkably clever computer software, we now know that 3.2 million years ago our ancestors were already walking upright. This suggests that we started walking upright when we were still living in the trees rather than when we’d moved down to the ground, as we previously thought!

I think this is a fascinating piece of research and the findings and potential applications are incredible, offering compelling evidence for how our ancestors have evolved. I look forward to hearing more about the group’s findings as their research continues.

Next up in this mini-series, we have a description of how ‘Personalised Medicine’ will work and how far away it is from being a reality. Come back next week for that one. Till then, have a great few days!

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Posted by on June 30, 2013 in Biology

 

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The Stem Cell – The Dorian Gray of the Bloodstream

Hi everyone! Apologies to those of you who follow me for the lack of postings over the past 2 weeks – things have been pretty hectic! However, as of now, I’m back on track and I’ll be bringing you 2 main posts this week to make up for the wait. This first one has been inspired by my reading Oscar Wilde’s ‘The Picture of Dorian Gray‘ – the story of a young man so consumed with his youth and beauty that he offers up his soul in order to retain his glory. I stumbled upon a research article into the damaging effects of ageing on the blood, which, given my reading material, struck a chord, so I thought I’d share what I read.

We all know that, as we get older, our bodies suffer – our bones become more brittle, we become weaker and, as I’ll discuss here, we become more susceptible to illnesses, including blood disorders. But why does all this happen? Well, for the most part, the cells from which we are made do not live very long. They are constantly dying and being replaced because of the countless toxins and physical pressures they have to cope with as they keep our bodies functioning properly. Imagine a weightlifter trying to hold his personal best above his head whilst someone continually punches him in the stomach and you’re probably on the right track! Replacements develop from special cells called stem cells. When first created, they have no specific function other than to make copies of themselves to maintain their numbers. However, stem cells have the potential to irreversibly take on the role of any other cell type when required. So, given this, why do stem cells don’t make us immortal? It is thought that their ability to function lessens over time, meaning that, eventually, fewer and fewer dead cells are replaced. The question is, in what way do they stop working?

Researchers at the University of California, San Francisco, have investigated this by looking specifically at stem cells made in the bone marrow – Haematopoietic Stem Cells (HSCs). These cells are responsible for replacing blood cells. When they don’t perform this role properly, as in aged individuals, numbers of healthy blood cells are reduced and unhealthy or dangerous cells and toxins become more prominent, resulting in blood disorders. This work aimed to understand why HSCs become less adept at producing healthy cells by studying their ability to carry out two essential cellular tasks: Autophagy and Apoptosis.

Autophagy involves sealing off, and breaking down, damaged or unnecessary cellular machinery. Normally, the resulting pieces can be used to build new machinery (like breaking down a Lego model to build a new one). During periods of starvation, however, they can be used as a source of nutrients and energy.
Apoptosis, meanwhile, essentially means ‘cell suicide’. Cells, including stem cells, that are severely damaged or unable to perform their given tasks can kill themselves.

The research group genetically engineered HSCs from mice so that they did not possess certain genes involved in these 2 processes – this is called a ‘gene knockout‘ technique. If a cell does not possess a certain gene then that gene cannot do its job. Scientists use this method to see exactly what roles individual genes play in a cell. The modified HSCs were exposed to both normal bloodstream-like conditions and those seen during periods of starvation. The group made the following observations (with the exception of the first one) by knocking out various genes and monitoring the effects they had on cell survival:

1. HSCs are far more capable of employing autophagy to react to starvation than other cells in the bone marrow. This is a well-known trait of stem cells.

2. Autophagy, as a process, exists to protect cells – if they can repair themselves then they don’t need to destroy themselves via apoptosis. As HSCs are excellent at launching autophagic responses, they can live and function longer than other blood cells before resorting to apoptosis.

3. HSCs possess a set of genes, which ensure that HSCs are always primed and ready to become autophagic quickly, to avoid starvation, damage and death.

4. Older HSCs are just as capable of launching an autophagic response as younger HSCs. In fact, it seems that the cells rely on the process to survive as they slowly lose the ability to uptake nutrients and produce energy.

This research proves to be something of a first step, rather than a full conclusion, in my opinion. We now know that autophagy is essential to stem cell survival and occurs properly, even in old age. However, that leaves us asking what happens – what breaks – in stem cells to cause them to slowly malfunction and die? Regardless, I hope you agree that this is a very interesting step closer to discovering why our blood system ages and deteriorates. I particularly like the idea that, as malfunctioning cells and harmful toxins build up and blood disorders become more likely, the failing HSCs remain obsessed with trying to keep themselves young, much like a certain Mr Gray…

 

This post was based on Warr, M. R. et al. (2013). FOXO3A directs a protective autophagy program in haematopoietic stem cells. Nature 494 (7437) 323-7.

 
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Posted by on February 27, 2013 in Biology

 

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