Thursday, 31 October 2013

The Matrix

The Matrix 

    
          Loboa, a materials engineer has developed a ‘self-destructing super-bandage’ that is capable of ‘healing infected wounds quickly, without scarring or standard antibiotics’. It is essentially a material that degrades until only your own regenerated, healthy cells remain; allowing for the concept to eventually heal damaged muscle, destroyed digestive tissue and even broken bone.
 
          Loboa’s work relies on the research into the extracellular matrix. This is the framework that ‘gives the various parts of our body their detailed shape and solidarity’, supporting and structuring the cells of a blood vessel or organ. However this isn’t its only function. Although the matrix chiefly consists of inanimate structural proteins, for instance collagen and elastin, it also comprises of proteins that essentially coax specific cells to be in a certain place. Once such animate proteins have induced the correct cells, the matrix then determines whether they become bone, muscle or fat cells, depending on the tension they experience once inside the matrix.
 
            In your body this tension is the consequence of the stresses of every-day muscle movement; high tension persuades stem cells to become muscle or bone whilst a matrix with a lower tension promotes fat cells. Another role of the matrix is to nourish the cells in order for them to mature into larger structures. This is the result of the matrix containing powerful growth factors that aids in the formation of blood vessels which subsequently provide oxygen for the developing organs. 

      It is the exploitation of these properties that have revolutionised the way in which both tissue and organs can be regenerated. The natural human extracellular matrix has allowed for the world’s first artificial kidney to be built courtesy of Harald Ott. Rather than using various stem cell types, only two cell types were essential in forming the organ. Blood-like stem cells were placed in the blood vessels of the decullularised kidney matrix whilst endothelial cells were positioned into the various sections of the filtering system - this ultimately caused the other kinds of cells to form in the sites they were supposed to.

          In terms of using the matrix to attract and grow muscle from a person’s own cells, this technique has already been successfully performed, primarily through the use of decullularised tracheas from corpses to create new fully functional tracheas.  In spite of this, its application hasn’t truly extended far beyond said method, and so a study has involved the matrix from a pig bladder being used to grow muscle in people who had lost more than half of a muscle in several types of trauma. Residual scar tissue was surgically cleared, and then a strip of the matrix was placed into the exposed void, made taut enough to indicate to the body that it should become muscle. Eventually the pig matrix becomes completely replaced by the natural matrix of the patient as well as healthy muscle.  The natural matrix can also be used to repair shattered bone. Research has suggested that a matrix made from human blood is the most effective mechanism, as it is essentially a highly concentrated blood clot which contains large amounts of growth factors that promotes bone repair.

         Nonetheless there are drawbacks to natural matrices. The issue of them not being naturally antimicrobial is a particular concern due to the risk of the wound being infected by the ever increasing number of drug-resistant superbugs. It is thus clear of the importance of a synthetic matrix that could ‘turn slowly into the patient’s own tissue without ever exposing the flesh beneath to microbes’.
  
         Loboa developed a biodegradable material using polylactic acid (often used in medical implants) and shaped it into fibres that mimicked the structure of skin. Such fibres can be made solid, porous of hollow; however a porous construction is preferred as it can be permeated with a variety of anti-inflammatory drugs and Silvadur – a substance that contains small amounts of silver ions lethal to most drug-resistant bacteria including MRSA. The material works in two phases: the first release overcomes all present bugs, and the second guard ‘leaks out’ slowly to destroy any other interlopers. Soon the scaffold or plaster disappears too, leaving only a small scar where the wound once was.

         Another benefit of a synthetic matrix is that it ‘can be used as a template to build body parts far stronger than those nature provides’. A treatment where this would be especially beneficial would be for kidney dialysis. A fast-decaying biodegradable polymer can be constructed into a tube exactly the same dimensions of a vein, but with a thicker vessel wall, and coated in human muscle cells. Within days the cells replace the tube with a matrix of natural collagen which is thicker and thus better able to withstand extra pressures of dialysis. After decellularisation, the tubes can be surgically implanted into the patient, serving as the vein for dialysis; thus eradicating the risk of the natural veins from collapsing.

         The potential for synthetic matrices is seemingly endless; nevertheless an artificial matrix does not have the countless properties of natural matrix, which will forever be crucial for building organs as ‘it retains so many factors to bind and differentiate cells’.  However, for some applications, hybrids are a possibility; a mechanism that incorporates both the artificial and natural matrices. For example, a synthetic matrix can provide a stronger scaffold, that can be tailored to requirements, i.e. providing extra ‘niches’ for cells, whilst a natural matrix can then aid wound healing through fibrinogen – to encourage the body to accept the component, the hybrid can then be coated with surface cells derived from the patient’s fat.


         There are other future possibilities for the matrix too. A multi-layered version could ‘simultaneously regenerate multiple kinds of tissues damaged in severe accidents ‘, and be potentially used by the military to treat war wounds on site at a lower cost. It even has potential for repairing brain damage; a signalling molecule released from the brain matrix that has been damaged by stroke, called DV, promotes the growth of new blood vessels. This molecule, once injected into mice who had suffered strokes, had entirely repaired the brain damage within only a couple of weeks. The promises of these discoveries appear infinite, and I hope it won’t be long before they become a reality.

Reference:

Monday, 28 October 2013

Anti-Quorum Sensing Molecules

Anti-Quorum Sensing Molecules: The Future of Bacterial Resistance


The misuse of antibiotics has meant that some bacteria have become resistant, such as strains like the ‘superbug’ MRSA, and has caused for extensive research to be taken into other methods that will prevent harmful bacteria. Although new antibiotics have been created from different microbes, they are a finite source for antibiotics and so are only a short term solution. However, Bonnie Bassler, a microbiologist has discovered the crucial element in the on-going war with bacteria; the way in which bacteria co-ordinate collective behaviours and function as multi-cellular organisms through a mechanism known as quorum sensing.

Quorum Sensing

   
      Quorum sensing is the bacterial communication phenomenon; during quorum sensing, bacteria produce, detect, and exchange signalling molecules known as auto inducers. The concentration of a particular auto inducer enables a population of bacteria to collectively regulate gene expression, thus meaning specific genes are only synthesized as particular population densities. This process is crucial to disease development because it ultimately controls the way that bacteria express virulence factors—the molecules that enable the bacteria to colonize a host. In bacteria, virulence factors are often encoded on mobile genetic elements, such as bacteriophages, and can easily be spread through horizontal gene transfer. Auto inducers bind to receptors in the bacteria, forming receptor:autoinducer complexes which bind to certain sites along the cell’s DNA, triggering the bacterium’s virulence genes.

Anti-Quorum Sensing

     
      Anti-quorum sensing molecules would essentially prevent bacteria from communicating by strongly inhibiting quorum sensing through binding to the receptors in place of the autoinducers, thus upsetting the process. Said compounds would be specialised to target specific receptors of a bacteria type, and thus by being unable to carry out collective virulence activities that are critical for enabling bacteria to stay in the host, the immune system would have more time to get eliminate said pathogens. 
       
       Recently, researchers from Princeton University and the Howard Hughes Medical Institute developed a molecule to block quorum-sensing in the bacteria Chromobacterium violaceum which has a close homolog to a bacteria that causes particular trouble for cystic fibrosis patients. Due to the effectiveness of the mechanism of anti-quorum sensing, many scientists are now investigating other bacterial traits that could be similarly exploited.


The Benefits

       
     Because anti-quorum-sensing molecules do not kill bacteria, only keep them from communicating, it is probable that bacteria would be less likely to develop resistance; nonetheless if a resistance does develop, it will be expected to progress far slower than resistance occurs in response to current antibiotics. Furthermore, ‘quorum-sensing antagonists represent potential lead molecules in the search for new antibacterial therapeutics’, and so coupled with the success in this particular field, it shouldn’t be too far in the future that this treatment becomes available for a wider audience.



Diagram to Show How Quorum-Sensing Occurs

References:

http://www.bnl.gov/newsroom/print/friendly.php?a=22674




Malaria Vaccine

Malaria Vaccine Available in 3 Years
 

    GlaxoSmithKline, a major UK drug firm, seeks to market the world's first malaria vaccine within three years. Promising testing results showed that the drug, RTS,S/AS01 (commercially named as Mosquirix) was effective in protecting young infants for up to 18 months, nearly ‘halving the number of malaria cases in children between five and 17 months old’. The vaccine was engineered using genes from the outer protein of the malaria parasite and a division of a hepatitis B virus as well as a chemical adjuvant (a substance or agent) to boost the immune system response; its funding has stemmed from £124 million from the Bill and Melinda Gates Foundation, and its development has been aided by GSK’s partnership with the PATH Malaria Vaccine Initiative.

   
      However, a major setback appears to be that the effectiveness of the vaccine wanes over time, only protecting fewer than 20% of children for 4 years. Despite this, because of the vast influence of malaria (660,000 people killed by malaria in 2010) the number of cases of the disease the vaccine can help is immense, and thus the vaccine ‘does not need to be fully effective to make a huge difference’. Nonetheless, the cost of issuing the vaccine is a major concern, with economics presenting a significant barrier to the distribution amongst LEDCs who rely on NGOs and charitable foundations. 


References:

The Daily Telegraph

Wednesday, 23 October 2013

Alzeheimer's Beaten?

The Turning Point in the Battle to Beat Alzheimer’s


       Scientists have acclaimed the discovery of a drug-like compound that acts in preventing brain cell death in mice for the first time.  It works by blocking a faulty signal in brains affected by various neurodegenerative diseases including Alzheimer’s and Parkinsons.  In debilitating brain diseases, the production of new, essential proteins is inhibited by an accumulation of amyloids (misfolded proteins). Such build-up of amyloids triggers the ‘over-activation’ of a defence mechanism which is essentially activated by an enzyme known as PERK, and ultimately stops the synthesis of proteins. Without the presence of proteins, the cells are unable to function and thus eventually die – leading to the symptoms of diseases such as Alzheimer’s.  The compound itself works by preventing PERK, and therefore allows for the restoration and continuation of production of proteins.
     
         The compound was tested on mice with prion’s disease, and it successfully ‘stopped the disease in its tracks’, reinstating some normal behaviours and preventing memory loss. However the compound also caused significant side effects such as weight loss and diabetes, which would be a serious concern for the elderly population who would most likely benefit from this treatment. Although Professor Malucci argued that it would ‘not be impossible’ to develop a drug that protected the brain without said side effects. The huge benefit of such a compound is that it can be given orally, and directs itself into the brain to prevent the disease, meaning it has great potential to be turned into an accessible medicine.

   
        For those who question the viability of whether the compound will translate into other mammalian brains, the professors argue that it hopefully will, as prion disease is the best animal equivalent of human neurodegenerative disorders. On the other hand, although the breakthrough was met with excitement by scientists, they said whilst ‘it is not a guarantee of an Alzheimer’s cure in the near future; it remains a significant proof of principle'. Other critics weren't as convinced and contended that ‘many a new treatment has fallen by the wayside making the leap between mice and man’. 


References:

i - 'Scienticts Hail 'Historic' Alzheimer's Discovery'
http://en.wikipedia.org/wiki/Unfolded_protein_response

Wednesday, 9 October 2013

Soylent - The Cure for World Hunger?

Soylent - The Cure for World Hunger?
 

  Rob Rhinehart, a 24 year old is pioneering a potentially world changing product branded as 'Soylent'. It is essentially a food substitute that supposedly supplies all of a human body's daily nutritional needs. It is, in effect a mixture of everything the body requires.  This list of ingredients includes vital elements such as iron,magnesium and copper as well as vitamins, minerals and macronutrients such as amino acids, carbohydrates and fat. Soylent also includes non-essential substances such as antioxidants in order to help prevent cell damage, and probiotics to maintain symbiosis between harmful and 'friendly' bacteria. Rhinehart has also experimented with nootropics (drugs, supplements, nutraceuticals, and functional foods that purportedly improve mental functions such as cognition, memory, intelligence, motivation, attention, and concentration) in order to allow the consumer to become fully sustained on Soylent alone.
            
       The project, however, didn’t come without its shortcomings.  Any minute change in the proportion of an ingredient can result in an illness which Rhinehart experienced on numerous occasions, when first tested, the formula omitted iron, which caused Rhinehart to report his heart had begun to race. In other early experiments, Soylent caused Rhinehart to have cardiac arrhythmia and burning sensations. There are other drawbacks too; it doesn't keep long after mixing with water which would make it entirely impractical for those living in LIDCs due to the lack of clean water. In terms of first world problems, most people would deem it unthinkable to only have Soylent for their way of food.
        
          So Soylent is not all perfect then? Well it’s not surprising that nutritional experts were quick to criticise it, deeming it as "dangerous", "ludicrous", and "a red flag for a potential eating disorder".  It does seem rather improbable that one could survive completely off a food substitute; sceptics arguing that in its present form, Soylent may lack some nutrients essential for normal body functioning and/or may fail to provide nutrients in appropriate proportions, potentially causing medical problems if used long-term. However Rhinehart has supposedly managed to subsist almost solely off Soylent for a total of seven months without any apparent problems. He argued  that ‘we need fruits and veggies, though – we need vitamins and minerals. We need carbs, not bread. Amino acids, not milk’; which is entirely reasonable. I admit, at first I was dubious at the prospect of a complete food substitute but it seems unfaultable, our body needs essential nutrients, and in their pure form, in the correct balance you avoid the toxins, allergens, carcinogens as well as waste that you get with conventional food, thus preventing an extensive array of illnesses, to name a few – diabetes, obesity and cancer.  Not only this but Rhinehart claims it slightly boosts the capability of the brain and says he feels far more alert and active.
           
      The reason I am particularly interested in this revolutionary development, however, is its potential to greatly benefit developing nations. Soylent can be mostly produced from the products of local agriculture  which means this could be a truly permanent solution for LICs.  At a world wide scale it would be immensely cheap to produce, Rhinehart suggests it would cost no more than $35 for one fully grown man per month to have a complete Soylent diet of 2500 calories a day. Not only this but due to the lack of excess substances, it means that the body produces less excrement -  this would be particularly beneficial for countries in the developing world, where inadequate sanitation is a prevalent source of disease. Concerning the environment, currently agriculture is having a colossal impact on global warming, cattle farming and rice paddies being amongst the major causes of greenhouse gases. These adverse effects on the climate would be greatly reduced if Soylent were to be produced instead.

     The only issue remaining is for Soylent to actually be funded and distributed through the help of organisations such as UNICEF, the World Food Program, USAID and Action Against Hunger. However with over $1 million in preorders already received for Soylent worldwide, it appears that the solution to "the future of food" may come to fruition sooner than anticipated.

Rob Rhinehart - Pioneer of Soylent


References: