Post 4: Synthetic Bio, CRISPR/Cas9, and infecting the body with a healthy immune response

To move forward with the project, the team has decided to focus on Multiple Sclerosis only and to research 5 different solutions that can all work together to cure the disease. Since we have a group of 5, we decided that each person can work on one specific version of a cure that focuses on one step of the autoimmune response that causes the body to attack itself, thus everyone has individualized and important job in the project. The idea behind 5 solutions is that there are so many steps in an immune response, and only focusing on one step to try to stop the attack has failed over and over again in the field. Either the treatment doesn’t work well enough, it only helps a little, or it doesn’t work at all. However, since the field is under researched and the treatments are under developed, creating five different solutions and pairing them together can greatly widen the scope of knowledge with MS and create a series of backup protection if any one of the five steps were to fail.

For my specific step, I will be focusing on the aftermath of an MS autoimmune attack, which is the last defense in our cure idea. Our idea for this step is using the technology developed like CRISPR/Cas9 that genetically modifies a genome in a bacteria or virus. If we were to gene edit a virus, and properly identify the genes in the human genome that remyelinate oligendrocytes and the myelin sheath, then we could edit out all the genes in a specific carrier virus that causes its own immune response and edit in the genes that causes myelination. Therefore, in theory, the virus would infect the human body with the “disease” of remyelination. We would have to pick a virus that focuses solely on the nervous system, and stays with you for life. It also has to have a long enough genome to accommodate human genes. A virus that fits that criteria for example would be the herpes simplex virus, and other than the problem that the idea of giving someone herpes to cure MS by nature has a pretty negative ring to it, it would theoretically be a feasible carrier virus.


Post #3: isolating and suppressing a specific immune response

In my very first post, I discussed how many autoimmune disorders are treated through immune suppressant drugs which can leave a patient susceptible to many other infectious diseases and infections. It is certainly not a perfect system, and scientists are now looking at ways in which to suppress only the sector of the immune system that is generating the autoimmune response. Researchers supported by the National Institute of Biomedical Imaging and Bioengineering (NIBIB) are looking at the natural methods the body uses to suppress inappropriate immune responses. Normally, when a cell dies through apoptosis, it releases chemicals that initiate a response from a type of cell called macrophages that absorb and deposit the dead cells’ antigens in the spleen into a pool of T-cells- some of the cells responsible for an immune response. Then the macrophages suppress any T-cells with the ability to bind to self-antigens to not have a negative autoimmune attack. Currently, the method being tested in mice is coupling myelin cells in subjects with multiple sclerosis (in which myelin cells cause an autoimmune response) with self-antigens that do not bind with T-cells. So far this treatment has proven to be extremely effective in halting the progression of the multiple sclerosis in mice, and the next step is clinical trials. However, cellular therapy is apparently very costly, time-consuming, and needs to be done in a high-tech facility, and thus progress with this research is going to be difficult. Still, this method of treatment is not specific to multiple sclerosis and is projected to be effective in many other autoimmune disorders and diseases like allergies, type I diabetes, and maybe even Rheumatoid arthritis

post #2: what is actually going down on the neurons

Multiple Sclerosis (MS) is an autoimmune disorder that causes the body’s immune system to attack the central nervous system (CNS). This immune response diminishes the myelin sheaths that surround axons and also damages the nerve fibers underneath the myelin. This attack results in lesions of the axons and eventually results in a lack of insulation for nerve signals. Without these myelin sheaths, the nerve signaling is either slowed or completely blocked. The signals cannot reach the brain quickly or effectively and basic motor function or signaling pathways become greatly compromised. If one were to think of wires that connect to a phone or computer: if the rubber insulating the wire was not there, the charge could disperse to other surrounding objects and make the ending result much weaker or non-existent.


However, this comparison is not completely analogous to multiple sclerosis as the main purpose of the myelin sheaths is not actually to provide insulation for incoming and outgoing nerve signals. Instead the myelin sheaths allow for the neurons to perform saltatory conduction to speed up the slower process of an action potential. In between each myelin sheath is a regulated space of bare neuron that exists only at a length of a few microliters. These spaces between the myelin are called the Nodes of Ranvier (NORs) and are essential to rapid signal transmission. Therefore, the myelin sheaths work in conjunction with the NORs in order to execute saltatory conduction. The word “saltatory” comes from the Latin word “to jump” or “to hop” and describes the process of the sodium and potassium ion charge transferring from one node to the next, thus exponentially increasing the speed of the action potential by decreasing the area through which the charge is conducted.


Action potential is a binary electrical process that occurs in the membrane of our neurons. At what is called resting potential, our neurons are polarized so that they are negatively charged within the membrane and the extracellular space is positively charged. Embedded in the membrane are potassium ion channels and sodium ion channels that open for K+ ions to slowly flow out while Na+ slowly flows in when given a small type of stimulus. This flow of ions causes the depolarization of the membrane and the decrease of the resting concentration gradient, and if the stimulus is significant enough to depolarize the membrane past the threshold, then an action potential will occur. When an action potential occurs, Na+ ions flow rapidly into the membrane while K+ ions flow rapidly out.


Saltatory conduction increases the rate of nerve transmission through action potential from 5 meters/second (11mph) to 150 meters/second (330mph).


The main problem with having this new multitude of unmyelinated nerve fibers (otherwise known as unmedullated) suddenly in the central nervous system lies in the fact that unmyelinated axons are used primarily for sensory nerve signals. These neurons are either unmyelinated or sparsely myelinated, as they travel at much slower speeds and create duller signals. This specific type of nerve structure, the peripheral postganglionic autonomic fibers, has a great deal to do with how our body feels pain. Everyone has stubbed a toe in the past, and the feeling we get at first is a quick shooting pain that then dulls down to a bearable throbbing. Those quick shooting pains are the doing of medullated axons called A delta fibers that send pain signals quickly to the brain, and the slow and dull pulsing pain accounts for the unmedullated fibers named C fibers. Unmyelinated axons are also much smaller and travel shorter distances.


The main goal that researchers are currently working towards is enabling the body to rebuild the diminished myelin and repair the lesions done on the axons and nerve fibers. The primary research being conducted lies in stimulating brain cells and nerve tissue to repair what’s damaged. However, a big issue of MS is that the axons do in fact repair themselves to some extent, but biologists do not understand what prevents full reparations in the CNS.

Intro to Autoimmune Diseases!

Our group is going to be focusing on autoimmune disorders as they are becoming increasingly common in society with each passing year. Due to environmental factors and society’s evolving mass-production based diet, the prevalence of disorders found in patients from as mild as a lactose intolerance to as severe as type 1 diabetes is increasing rapidly. Type 1 diabetes rose 23% from the year 2001 to 2009. Quite simply, the main goal researchers are working towards is how to convince an overactive immune system to calm down. The primary treatment options today don’t usually involve getting the immune system to behave correctly, but instead most autoimmune care simply makes your immune system weaker. Therefore, the immune response is not as bad, but the individual is now more susceptible to other diseases and viruses. We are not entirely sure why some people acquire autoimmune diseases and others don’t, but there are some identifying patterns: women tend to have them more than men at a rate of about 2 to 1, Caucasians are less likely to have lupus than Hispanic and African American people, and autoimmune diseases are often genetic.

I have a personal attachment to autoimmune diseases as my brother, Sam, was diagnosed last year with a mild case of multiple sclerosis: a disorder in which your immune system attacks the Myelin sheath and oligendrocyte cells surrounding and protecting your peripheral and central nervous system. A year before Sam was diagnosed I did a research project in which I created a theoretical cure for MS. My cure included using the theoretical process of gene editing to reprogram the cells of the Myelin sheath to regenerate after a negative immune response as those responses for MS patients can be incredibly disabling for weeks to months at a time. Luckily, Sam is not likely to ever become extremely disabled from his disease, but 50% of all MS patients will need help walking about 15 years after their diagnoses. Gene editing will not only help fix the problem, but it will also help identify the problem in the first place as autoimmune diseases are notoriously hard to diagnose. Another autoimmune disorder we will be looking at is rheumatoid arthritis which attacks your joints and can cause mild to severe immobility. Autoimmune diseases are very important to study and try to cure as developing cures for people whose immune systems do not work properly can also lead us to develop ways to make healthy immune systems even stronger.