Sofia

Hi, I'm Sofia! I'm 17 years old and a rising Senior at Newton North High School in Ma. I'm a major history nerd who also has a passion for biology. I love to travel, I have lived in London and visited France, Israel, and Jordan among other places. I cannot wait to travel more extensively and would love to spend more time in the Middle East and to visit Southeast Asia, India, and Sub-Saharan African countries. Basically, a plane ticket to anywhere would make me incredibly happy!

I recently discovered my passion for the sciences, especially biology and engineering. I have taken Physics, Chemistry, and Biology as well as basic engineering. In my Senior year I'll be taking AP Bio, Forensics, and TA-ing for my Chemistry/Biology teacher.

I'm interested in pursuing a STEM career and would really enjoy being a medical doctor either in pediatrics or a specialty that allows me to administer hormone therapy and counseling to transgender patients undergoing transition.

__ **Design Project** __



I. Purpose
White blood, or leukocyte, cells protect the body from infection. However, many people suffer from white blood cell disorders that skew the numbers or function of their leukocytes. This system looks to combat the issue lymphocyte deficiency. [see Fig. 1] Lymphocytes are produced in the bone marrow from stem cells, but mature in the blood stream. Lymphocytes, necessary for the body’s immunity, develop into two kinds; thymus cells (T cells) and bursa-derived cells (B cells). According to the American Society of Hematology, “T lymphocytes help regulate the function of other immune cells and directly attack various infected cells and tumors. B lymphocytes make antibodies, which are proteins that specifically target bacteria, viruses, and other foreign materials.” The system proposed is designed to release colony stimulating factors (CSFs) to encourage the process of lymphopoiesis, the specialization of lymphoid cells. It could be useful not only in treating hereditary and autoimmune disorders that cause a person’s lymphocyte count to be low, it could also benefit patients undergoing treatments such as chemotherapy or radiation therapy that include a drop in lymphocyte count as a side effect. By encouraging lymphocyte production this system could reverse the effects of autoimmune diseases and strengthen the immunity of this with weakened systems. Although this system is not perfect, and does not deal with disorder like lymphoma (where the lymphocyte count is too high) it does seem feasible that the additional research and deeper understanding of how white blood cells interact with each other that would be needed to perfect this system, could lead to breakthroughs in dealing with disorders where the patient has too many. The “normal” percentages for T and B lymphocytes are demonstrated by Fig 2. using these percentages, a physician could compare the patients levels and use this treatment to administer the appropriate colony stimulating factor (CSF) for the patient’s needs.  Designed to react to the interleukin signaling employed by white blood cells, this system should increase output of specific leukocytes based on the needs of the patient. The chassis of pleomorphic bacteria cells, which are native to the bloodstream and not in any way dangerous or invasive, will distribute colony stimulating factors (CSFs) specific to the needs of the patient.

II. Competing technologies
The issues resulting from T and B lymphocyte deficiencies are varied in terms of severity, therefore treatments vary as well and often depend on the time of diagnosis. Deficiencies in T and B lymphocytes are immunodeficiency disorders, so at the first sign a patient is given antibiotics to treat the infection brought on by the patients weakened immune system. These infections can range from mild (easily treated with antibiotics) to much more virile and long lasting infections. Additionally, low lymphocyte levels can accompany more complicated diseases or be a side effect for invasive treatments. Therefore, this drug could not only function as a treatment for autoimmune disorders but could also accompany treatments such as radiation therapy, chemotherapy, or steroids.  At this time there is no cure, and the only available treatments are assorted therapies aimed at controlling or limiting infections and, in some cases, replacing missing compounds. Less severe cases sometimes repair themselves as is demonstrated by some patients with DiGeorge syndrome whose thymus has repaired and generated more T lymphocytes independently or with minimal therapy. Often, however, this regeneration is not the case and intensive bone marrow or thymus transplants are necessary.  Bone marrow and thymus transplants are often successful, but are labor intensive, painful for the patient and donor, and are often limited by the donor supply. The design proposed would be an attractive alternative to these procedures as it would not present the same issues of donor availability and match as the treatment would be generated on a patient by patient basis and would, most likely, be administered through injection.

III. The design

 * Transcription Factor || Inhibitor || Promoter || CSF || Transporter ||

his design would allow a pleomorphic bacteria (naturally occurring in the human bloodstream) to release colony stimulating factors which encourage the production of specific lymphocytes. Because this device would be used in patients that have low levels of white blood cells, it would react to the interleukins that leukocytes use as a sort of intercellular signaling mechanism. There are over 20 varieties of interleukins that have been and, as far as my research covered, 4 or 5 types that would be viable options. I have black-boxed the specific interleukin and, were this device to be developed for use, research and consultations with hematologists would need to be done to ensure the interleukin used for this device would be the most effective and would be released largely by the lymphoids I am looking to count. There are, however, systems already designed off interleukins such as interleukins 7 (see Fig. 3) so it seems viable that this or similar systems could be adapted to my device. The genetic expression would be affected by the amount of white blood cells already existing. The doctor administering the drug would assess the patients lymphocyte levels and, from there, determine the amount of bacteria necessary (this is assuming that in lab work direct percentages of CSFs released per bacteria were determined). This data could then be compared to the amount of interleukins in the blood stream which is representative of the number of leukocytes. Therefore, the scale of genetic expression would be responsive to the scale on which it was needed. The greater amount of interleukins means less need for colony stimulating factors because, one could assume, there is a good amount of viable lymphocytes. On the reverse, low levels of interleukins would signal the system to produce more CSFs which would help the existing white blood cells develop into the necessary lymphocytes. IV. The parts 1) Interleukins-**black-boxed** because further research would need to be done to determine the optimal interleukin for this purpose (there are currently over 20 identified interleukins) 2) Inhibitor that binds when specific interleukin is present- **black-boxed** as well because interleukin would need to be identified before inhibitor could be discovered or developed 3) promoter- chose to use **lac promoter** because it is well understood and could be easily applicable for each CSF sequence <span style="font-family: 'Times New Roman',serif;">4)genetic code to produce colony stimulating factors- different companies and resources such as genecards, sabiosciences, ucsc genome, BETA geneIP, giagen, and others have optimized genetic sequence for the each CSF. <span style="display: block; font-family: 'Times New Roman',serif; text-align: center;"> <span style="font-family: arial,helvetica,sans-serif; line-height: 1.5;">] <span style="font-family: 'Times New Roman',serif;">5) transporters- these are two possibilities for transporters that could theoretically disseminate the CSF to the blood stream. <span style="font-family: 'Times New Roman',serif;"> 1) BBa_K103006 <span style="font-family: 'Times New Roman',serif;"> 2) //SLC7A9// <span style="font-family: 'Times New Roman',serif;">7) the chassis-pleomorphic bacteria

<span style="background-color: #ffffff; color: #800080; font-family: 'Times New Roman',serif;">V. Expected results
<span style="font-family: 'Times New Roman',serif;">Under ideal circumstances, the cell will produce the CSFs regularly when not inhibited by interleukins and will be properly inhibited in the presence of interleukins. This includes getting the correct ratio and making sure that there is not overproduction of CSFs. <span style="font-family: 'Times New Roman',serif;">These results, assuming the device works as it should, will be a successful solution for patients lacking lymphocytes or lagging in lymphocyte production. By creating a system that exists in the bloodstream and relies of the signals of the patient's existing leukocytes, the device will be minimally invasive and will, hopefully, be a permanent solution that can be monitored by medical professionals to ensure a proper number of CSFs are produced. As well, this device only takes one injection to put in the patient (much less painful and labor intensive than marrow grafts) and is one the whole easier and more customizable to the needs of the patient.
 * Interleukin || sensor || promoter || CSF || WBC production ||
 * 0 || 1 || 1 || 1 || 1 ||
 * 1 || 0 || 0 || 0 || 0 ||

<span style="background-color: #ffffff; color: #800080; font-family: 'Times New Roman',serif;">VI. Potential problems
<span style="font-family: 'Times New Roman',serif;">Many of the problems identified come from a lack of understanding of interleukin signalling, especially in lymphoid progenitors, and would be resolved by the research that would be done to develop, construct, and perfect this device. <span style="font-family: 'Times New Roman',serif;"> Additionally, one would need to further research and perfect a cell death mechanism that couldbe employed in the case of overproduction. It would be irresponsible to test this device, or even think about human implementation without the perfection of a system that would perfectly protect against overproduction which could lead to blood cancers like lymphoma. Early studies of this bacteria have found that it is responsive to certain antibiotics (Polymyxin B being the most inhibitory, bacitracin having limited effects)

<span style="background-color: #ffffff; color: #800080; font-family: 'Times New Roman',serif;">VIII. Testing
<span style="font-family: 'Times New Roman',serif;">A lot of testing would be necessary not only to perfect this device, but to check its safety for public use. The preliminary testing would be dedicated to the interleukin signaling, as well as the effectiveness of CSFs for this purpose (some research indicated that certain interleukins-those not involved in signaling- could be more optimal). Once the devices were perfected and the plasmid has been transmitted into the pleomorphic bacteria in vitro the system would need to be tested in vivo. This would definitely involve animal as well as human testing once the device was perfected. This testing would not only perfect the system but allow scientists to learn more about inter-leukocyte signaling and thus allow advances in treatment of blood disorders. Figure 1: [|http://almostadoctor.co.uk/content/systems/haematology/haematopoiesis-blood-cell-] Figure 2: [] Figure 3: []

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