Proceedings of 2009

Harlem Children Society Workshop & Lecture Series #3

July 21^st 2009

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On Tuesday, July 21^st 2009, the third seminar in the Harlem Children Society (HCS) Summer Internship Weekly Series was held in Caspary Auditorium of Rockefeller University. Dr. Sat Bhattacharya opened the program by officially greeting and introducing special invited guests Dr. Robert Darnell, Dr. J. Paul Martin, and Mr. Errol Cockfield. Dr. Sat then provided a brief description of the HCS Weekly Lecture Series for the benefit of the guests and introduced the first of the guest speakers, Dr. Robert Darnell. 

Dr. Sat spoke of Dr. Darnell’s work as a Robert and Harriet Heilbrunn Professor in Cancer Biology at the Rockefeller University, Head of the Laboratory of Molecular Neuro-oncology and Director for Science Programs at Rockefeller University Hospital. An investigator at Howard Hughes Medical Institute, Dr. Darnell also holds appointments at Weill Medical College of Cornell University and Memorial Sloan-Kettering Cancer Center. Having received his undergraduate degree in biology and chemistry at Columbia University and his M.D. and Ph.D. degrees from Washington University School of Medicine, Dr. Darnell trained in internal medicine at Mount Sinai Medical School in New York and in neurology at Cornell University Medical School. Dr. Darnell’s awards include the Burroughs Wellcome Fund Clinical Scientist Award in Translational Research in 2000, the Derek Denny-Brown Young Neurological Scholar Award in 1998 and the Irma T. Hirschl Career Scientist Award in 1996.

Dr. Darnell took the podium to present his talk entitled, “Rare Diseases as Rosetta Stones… developing a new approach to understanding life and death.” He opened by saying that it was inspiring for him to be speaking to the HCS students, and that…” the best ideas often come from young minds. They are important to the life blood of creativity in the laboratory.” Dr. Darnell then emphasized the importance of keeping focus on the big picture in science.

The doctor then spoke about how his lab works on diseases that are considered esoteric, and he defined the word for the students to give them context. Dr. Darnell then gave the students a bit of history in conjunction with curing major obscure “esoteric” diseases. The first breakthrough he pointed to was the story of how mold had been observed and resulted in the discovery of penicillin.

Dr. Darnell turned to speaking about the Rockefeller University Hospital, a research facility with 35 beds, where patients need only have diseases that are being studied by Rockefeller faculty members in order to be admitted and treated on a pro bono basis. He said it was there that Oswald Avery, Colin McLeod, and Maclyn McCarty, renowned Rockefeller research physicians made another ground-breaking discovery in 1944: DNA. Of course, this led into Dr. Darnell’s discussion of DNA in connection with cancer, and cell mutations.

The doctor then spoke about the body’s immune system and the fact that it naturally recognizes when something is wrong, and is therefore able to fight disease, as in the case of many viruses. Dr. Darnell posited that if the body can recognize a virus, why wouldn’t it be able to recognize cancer and fight it as well? He then quoted Sir Lewis Thomas and William Burnet’s 1957 Tumor Immunosurveillance Hypothesis: “It is by no means inconceivable that… Tumor cells may develop... new antigenic potentialities (to) provoke an effective immunological reaction with regression of the tumor and no clinical hint of its existence.” 

Dr. Darnell then posed the following idea: Suppose our bodies get mutated cells in large numbers at all times, and maybe our natural defenses naturally recognize cancer, and get rid of it. How would we know it? There would be no clinical evidence of its existence. As an example, he referred to the number of smokers who do not get lung cancer…. Or do they? Perhaps these people’s immune systems are fighting the cancer naturally. 

To demonstrate his statement, Dr. Darnell then screened a clip from the popular television show, “House,” in which a female patient is exhibiting neurological abnormalities and is being diagnosed. Dr. House asks his team if the patient has been tested for breast cancer after eliminating several other suggested diseases.

Following the film segment, Dr. Darnell went into “paraneoplastic neurologic disorders (PNDs), a group of diseases thought to arise when tumors in the body — typically breast, ovarian or lung cancers — begin to make proteins that are normally made only by the brain. Patients with PNDs carry very high amounts of antibodies specific for the neuronal proteins, a situation associated with an effective antitumor immune response but also to an autoimmune attack on brain tissue.”  Esoteric or not, he asked?

Dr. Darnell then showed footage of actual cancer patients, but rather than exhibiting typical manifestations of cancer, their immune systems are fighting the disease and manifesting symptoms in terms of neurological malfunction (muscle control in the cerebellum). He compared these cases to the rare Rosetta Stone.

He showed another slide depicting the case of a lung cancer patient whose body had clearly fought the disease with immuno-response, and it was evident that the cancer was eradicated. Dr. Darnell went back to the discussion of the female patient with breast cancer exhibiting neurological malfunction as “the patient that got me hooked.” He expressed how the work with this patient had allowed him to clone genes making PND antigens.

Displaying antigens associated with lung cancer and breast cancer, the doctor then pointed out scientists could obtain the genes and how this would translate into valuable research. It would allow researchers to try to better understand the nature of the disease and how to better treat cancer.

Next, Dr. Darnell gave a bit of background on the human immune system. He explained the role of killer T-cells, proteins (antigens) and the receptors that recognize proteins within cells. He gave an example of how virus is recognized by T-cell receptors, which induce diseased cells to commit suicide. Dr. Darnell then turned to the lymph nodes controlling T-cells, and mentioned how that research, too, had taken place at Rockefeller University. He spoke about the instructors within the lymph nodes to license T-cells, aka, dendritic cells, to kill cells in the body.

Dr. Darnell’s lab is asking basic questions about what goes right and wrong in the immune system to allow these responses to develop: How are these neuronal proteins recognized as foreign by the immune system in tumor cells, and why in only some patients does this turn into an attack on nerve cells? Why do some patients react to tumors expressing these neuronal proteins, but others do not?

It was through a seminar on Lupus (another autoimmune disease) by Anthony Rosen and his wife that Dr. Darnell gained insight. He pointed out the mechanism of how dendritic cells eat dead cells. They actually scatter and sniff out suicidal (apoptotic) cells. The dendritic cell then packages them and takes back the apoptotic cells (“gatekeeper cells”) to the lymph nodes and gets permission to send more killer T-cells.

“Through their work, Dr. Darnell’s lab has shown that PND patients react to tumors with a classical anti-viral type of immune response. PND patients produce both antibodies and T-cells specific to the neuronal antigens found on their tumors, suggesting that an understanding of how the immune system is activated in these patients may provide a route to a potential cancer treatment. Based on the tumor immune responses observed in PND patients, Dr. Darnell’s lab has discovered that apoptotic tumor cells can serve as potent instigators of the killer T cell immune response in PND patients.”

The doctor spoke of his lab’s “…clinical research studies being performed at The Rockefeller University Hospital to help scientists better understand the underlying mechanism responsible for this effective tumor immunity, and to mimic it by developing experimental cancer vaccines. “

Finally, Dr. Darnell revisited his earlier statement pertaining to keeping focus on the big picture in science. He underscored how the big picture of DNA in the 20^th century as the key molecule is, in the 21^st century becoming replaced by RNA as the key molecule. Dr. Darnell has also become interested in the role of RNA binding proteins in the brain and in disease. He is exploring the function of neuron-specific RNA binding proteins in neuronal biology and in disease. The functions of two proteins in particular, the PND antigen Nova and the related protein FMRP — the protein mutated in Fragile-X mental retardation — have been explored.

The lab’s goal is to identify the RNAs that are regulated by these and, more generally, by a larger group of such proteins. New techniques are being developed with this goal in mind. These have been used to identify a network of more than 100 alternative exons within mRNAs made in the brain whose splicing is controlled by Nova, and are now being applied to FMRP and other RNA binding proteins that are involved in neurologic diseases. Dr. Darnell’s lab is interested in exploring the possibility that RNA binding proteins like Nova may act to change RNA metabolism in tumors.

The new techniques have provided a set of known Nova targets, and Dr. Darnell’s lab is now working to determine how that group is defined and how it functions. This research led to the discovery that the set of mRNAs regulated by Nova is involved in synaptic function, and is defining a new relationship between the regulation of RNA complexity in the nucleus and complexity in the synapse itself.” (http://www.rockefeller.edu/research/abstract)

After Dr. Darnell had concluded his presentation with a question and answer period, Dr. Sat introduced the first HCS student presenter of the day, Rodney Agnant. In his reprise presentation entitled “Advanced Conformational Analysis: Molecular Mechanics vs. ab initio.” Rodney, HCS class of 2007 and a senior at Brooklyn Technical High School, spoke about his summer 2008 research under the mentorship of Dr. Steven M. Graham at St. John’s University. He discussed cADPR (cyclic Adenosine Diphosphate Ribose), an organic molecule that contains both rings and chains that are able to move and important in regulating many cellular processes, including calcium signaling.

In outlining his purpose and hypothesis, Rodney first mentioned that there are over 100 known analogs of cADPR, and that he had been interested in determining how conformation determines function, investigating the effect of charges on conformation and energies, and testing 2’dA and F3”ddA molecules. In analyzing north, south and overlapping conformations, he used the classic model, molecular mechanics, and ab initio, quantum mechanics, as well as the structure analysis program, HyperChem 8.0.4.

Rodney’s procedure had involved editing two molecules from the database, calculating energies using Ab Initio 3.21G*, applying Amber 99 Molecular Mechanics, and building twenty conformations (for each molecule). Next, the process had involved extracting the ribose ring (f_CCC/O) and H-H angles (f_HCCH), and finally plotting energies as function of the phase angle of the conformation(s).

Rodney displayed several graphs of his results and concluded that ab initio charges had improved results and created a series of more stable conformations. He had found that the F3”ddA may prefer gamma minus except for a few North conformations. Further to his discussion, Rodney qualified his research saying that the information is only theoretical since its all via computer, and that the initial conformation may affect the function. In the future, he would like to test more complicated molecules, especially in connection with Ryanodine receptors. Rodney would like to look into the potential applications; particularly the medicinal uses for cADPR and its role in regulating heartbeat, and correspondingly explore the medicinal uses.

Dr. Sat returned to the podium and announced that students who had submitted high quality write-ups would soon be acknowledged on the program for their hard work this summer. He also mentioned that just as hard work is important, so is taking a break. With that, he launched into his discussion of the upcoming Third Annual HCS Science Boat Cruise on August 6^th.  Dr. Sat introduced Prof. D. Jeanne Ross to share information about the event, and her remarks were followed by an audiovisual presentation featuring photo highlights from the prior year’s cruise and produced by Alejandro Naranjo, HCS IT staffer.

Next on the program, Mr. Errol Cockfield, Jr., special guest and Governor David Patterson’s Senior Advisor for Inter-governmental Affairs in New York City, was invited to the podium to briefly address the HCS students. In his speech, Mr. Cockfield stated that on behalf of the Governor, he was pleased to be a guest of Harlem Children Society. He commented about the importance of programs like Harlem Children Society, and that he was happy to be seeing it firsthand. “…We recognize that New York and the U.S. have fallen behind in the sciences on the global stage. We think these programs and partnerships are so important. … Even at a time when the state is hurting financially, and Wall Street has been hit very hard, we’re still finding creative ways to support partnerships like this.…  I’m here to let you know that I’m going to fight very hard to make sure that this work continues….”.

Following the address, Dr. Sat spoke about Mr. Cockfield’s background. A native of Georgetown, Guyana, Mr. Cockfield had graduated from Stony Brook University with an English degree. He had had several stints as a reporter for the LA Times, Hartford Courant, and Newsday. After eventually having become Newsday’s Albany Bureau Chief, he was appointed in 2007 by then-Governor Eliot Spitzer as Downstate Press Secretary to the Empire State Development Corporation. Shortly thereafter, Mr. Cockfield had been promoted to Press Secretary, and remained in that position until recent events landed him in his current capacity as Senior Advisor to Governor Patterson in Inter-governmental Affairs.  

Dr. Sat went on to describe the HCS programs in New York City, as well as in other cities and rural areas of the United States. He elaborated on the HCS programs across the globe, and the thread of global competition in the context of the 21^st century. But more importantly, Dr. Sat delved into the notion of internal competition and working with others to build a legacy. “…Internal competition leads man to ownership of society, and whatever we do in life, we must leave it behind, and that is our greatest gift to humanity.”  

Following his speech, Dr. Sat presented awards to all three invited guests. Mr. Cockfield received the HCS Harlem Dream Award. Doctors Darnell and Martin were both presented with the HCS Science and Society Award. Upon Dr. Darnell’s receiving the award, he poignantly added, “If you love what you do, you don’t have to work a day in your life.”

At this point in the program, Dr. Sat spoke about special guest speaker, Dr. J. Paul Martin, Professor and Director of Human Rights Studies at Barnard College. In his introduction, Dr. Sat first highlighted Dr. Martin’s particular interest in Africana studies.

Professor Martin's professional experience has been built around his 29 years as executive director of Columbia's Center for the Study of Human Rights, of which he was a co-founder. Prior to being executive director, and later simultaneously, he was director of the Earl Hall Center at Columbia University; lecturer in the School of International and Public Affairs; and adjunct professor at Teachers College. Dr. Martin has also served as director of the Human Rights and humanitarian affairs concentration at the School of International and Public Affairs, as well as academic advisor for the human rights concentration in the master's program of the Graduate School of Arts and Sciences.”

Dr. Sat mentioned that prior to coming to Columbia for his Ph.D., Professor Martin was dean of residence and lecturer at the then new University of Botswana, Lesotho, and Swaziland in Lesotho.

The HCS President then invited the guests to the podium to assist in presenting awards to HCS students for their outstanding achievement in writing their HCS Weekly Lecture Series reports. Dr. Sat also invited HCS staff member Caty Santos to the podium. She briefly spoke about her two mentors: Dr. Paul Martin and Dr. Sat. Ms. Santos had met both gentlemen in her hometown of Monterrey, Mexico while working at the Universal Forum of Cultures.

The students recognized were: Mai Abdelal, Marwan Abdelal, Mavis Addai-Mensah, Farzana Ahmed, Givi Basishuili, Kenneth D’ Silva, Dalibell Ferreira, Briani George, Roberta Greenslade, Monique Honeyghan, Whitney Lai, Nikida Levy, Mojolaoluwa Mabayoje, Xavier Marrero, Yeboah Naa-Akomaah, Guanpeng Ou, Caramina Perea-Chamblee, Kedarry Ransome, Docia Sakyi, Victoria Saldina, Nino Sanadze, Ivan Schoop, Dominique Smart and Hafsa B. Yucel.

Following the student awards presentation, and photos, the entire HCS student body posed for group photographs. Dr. Martin then approached the podium to address them.

Dr. Martin began his talk by asking the HCS students a few questions about Liberia, the focus of his talk. He posed questions related to politics and geography, and its connection to the United States. He explained that Liberia sees itself as having a very special relationship with the U.S and was formed as the “51^st state” of repatriated slaves, aka “America Liberians.” 

He then turned his line of questioning to science, asking students to identify diseases that might be prevalent in Liberia. Students suggested tuberculosis, HIV, African Sleeping Sickness, meningitis, cholera, typhus, and measles, among others. Dr. Martin pointed out the overwhelming health issue of maternal mortality.

Prof. Martin then provided background on a short film that was to be presented, “Iron Ladies of Liberia.” The film is a documentary about the first female Liberian president, Ellen Johnson Sirleaf. Upon election, and despite support both in Liberia and abroad, Johnson Sirleaf was faced not only with reforming a corrupt authoritarian government saddled by astronomical debts, but also confronting opponents loyal to former President Charles Taylor. This required executing a delicate balancing act to avoid alienating her voter base.

Dr. Martin explained that the film goes behind the scenes of Sirleaf’s largely female administration during its first year, as it works to prevent a post-conflict nation from returning to civil war. He outlined some of the infrastructure issues the administration faced, and asked the HCS students to try to identify human rights abuses in the excerpt of the film they were about to see.

Immediately following the film, Dr. Martin returned to the podium and immediately spoke about Liberians and their right to education. He delved into the destruction of schools in connection with civil war. The United Nations, upon entering the country on peacekeeping mission had discovered the deplorable conditions, and painted a dismal picture. Dr. Martin spoke about the lack of buildings, equipment, textbooks, and teachers. 

Further, Dr. Martin went into the prevalence of illegal weaponry in the hands of young people as a means of manipulating them into creating havoc under the guise of empowerment. He drew the connection to other African countries in this respect, as well.  He stated that violence and use of violence are undermining Africa’s development. Developed countries use the continent as their marketplace in peddling their arms to them. Because of this proliferation, there is always the danger of civil war.

Prof. Martin then turned to the monumental difficulties in creating employment. He went into tangential issues, such as lack of electricity, telephone systems, and sanitation. As depicted in the film, he pointed out how the government had faced civil unrest as it tried to clear the streets of marketers to make way for traffic. The profession of taxi driver is one of the few viable professions available, and if this is to remain so, cars must be able to circulate on city streets along with other vehicles.

The professor described Liberia as a country “hovering” above civil war. He discussed how it is crucial to encourage people to stay in Liberia rather than immigrate, as people with promise normally wish to do. A stable and responsible citizenry is a critical element to cement the success of Liberian (or any) society.

This led to Dr. Martin’s discussion of corruption, and the current trial of Charles Taylor in The Hague. He further illustrated problematic scenarios, including science-related issues. Quality health care is problematic as is keeping healthcare providers in country.

In concluding, Dr. Martin tied together the importance and role of science research to increasing the body of knowledge as well as solving problems on the ground. Dr. Sat approached the podium and added his comments about the work of HCS students in studying nutrition as an example of work on the ground. He put the students to task, saying, “You’re the next generation and the question is how you will place your emphasis and use your skills.”

Dr. Martin further suggested that students could potentially help with Liberia’s problems by going there and working within the healthcare system or laboratories. He also emphasized that in order to be truly effective, the young scientists of HCS must also write and speak well.

In connection with the discussion, Dr. Sat invited Mrs. Elizabeth Mtui, the first female engineer of Tanzania, from the audience to speak about problems in her own country. Mrs. Mtui recounted the difficulties of growing up in poverty, her perceptions of such, and how she had personally dealt with the situation. She closed by saying that if the students worked hard, they would have the chance to change the world.

Dr. Sat echoed Mrs. Mtui saying, “Take very seriously each opportunity you have to learn who you are. It’s your duty to feel responsible. We arm ourselves with education rather than guns.”

In several final comments, Dr. Martin expanded on the idea of conflict resolution, pointing to a positive example in Africa: Ghana. He discussed the gentle nature of the population there, and how it has served them in maintaining stability and peace. Advising the students to examine their own conflict resolution skills, Dr. Martin underscored that those skills are vital to any type of healthy relationship, whether it be with family, spouse, social or professional. In closing, the professor stressed the importance of mentors and their abilities to open doors for students. Dr. Martin concluded with, “Don’t be afraid of your dreams, but you need help to get them.” With that comment, the program broke for lunch recess.

As soon as the group reconvened, Dr. Sat made some organizational announcements and introduced student presenter, Alberto Del Rosario, HCS Class of 2004, and a senior at Stony Brook University. Under the mentorship of Dr. Michel Sadelain and John C. Markley at Memorial Sloan-Kettering Cancer Center, Alberto, now in his 6^th year at HCS, had worked on his research entitled “Cloning of recombinant expression vectors that encode Interleukin-15 (IL-15), Interleukin-21 (IL-21) and Luciferase for tumor immunology studies.”  

Alberto’s experimental objectives had been to produce HIV-derived retroviral vectors that would allow T-cells to express Luciferase and IL-15 or IL-21. Second, he had wanted to produce T-cells that artificially express cytokines in order to learn more about their effects on T-cells in the setting of tumor immunology.

The student next explained the importance of cytokines and the role of Luciferase in his experiments. Cytokines help T-cells to better eradicate cancer cells, and are therefore vital to cancer treatment. Cells that express Luciferase produce light when luciferin (the enzyme’s substrate) is injected intravenously. The light can be detected via infrared camera. The role of Luciferase thus allows the tracking of T-cells in the living body of the mouse.

Alberto’s experimentation involved using plasmids and restriction enzymes to first produce a final vector of IL-15. Through further similar experimentation, Alberto was able to produce PCR (Polymerase Chain Reaction) results that showed the desired band (at 508 base pairs). The sample was then cut and the DNA extracted from the agarose gel. Alberto displayed a slide that represented the cDNA of human IL-21 that was produced.

Following Alberto’s experiment in cloning the desired genes, Alberto’s mentor was going to make lentiviral vectors. He would then transduce T-cells with these vectors and inject “knock-out” mice intravenously with the transduced T-cells. The mentor would then monitor the mice on a weekly basis measuring tumors to see if they were eradicated.

Alberto commented that while Il-15 had gotten off to a slow start, it had improved in efficacy. Though IL-21 had started out well, it had diminished in its effects. The student concluded that using cytokines provides an effective method of fighting cancer, but there are marked differences in ILs and their effects. In the future, Alberto stated he would like to continue testing other ILs to determine those most effective in eradicating cancer.

HCS staffer, Rishesh KC, approached the podium and introduced the next student presenter, Morkous Hanna. In his talk entitled “Random Motility Analysis In ABI-1 Knockout Mouse Embryonic Fibroblasts (MEF),” Morkous, HCS Class of 2007, and a student at Grover Cleveland High School presented his summer 2008 research under the mentorship of Dr. Patrycja Dubielecka and Dr. Leszek Kotula in the Cell Signaling Laboratory at the New York Blood Center.

The student first defined cell motility in his background discussion. He explained that cell motility is the method that single-celled organisms use to both move in their environments and move things internally within the cell. Different types of cells use a variety of strategies to move in order to seek food, produce energy, avoid death and fulfill functional roles. In multicellular organisms, cell motility enables single cells and cell groups to migrate in the embryo to appropriate locations in the developing body. Unfortunately, this same process, critical to physical development, may become deadly when uncontrolled. Unrestrained cell motility may lead to cancer and the metastasis of cancerous cells.

Morkous then went on to discuss how motility is measured. The student used a manual process of imaging that is subject to variable interpretation. He used a Zeiss Meta 510 confocal microscope connected to a CO₂ atmosphere-regulated incubator to visualize cell movement, and Image J software to directly measure tracks generated by migrating cells.

The student then stated that a cytoskeleton was needed for cell movement and showed a diagram of a complex controlling acting polymerization in a cell. This led into the student’s hypothesis: ABI-1 is found among the major proteins required for the control of the actin polymerization-depolymerization process and its removal or any of the actin polymerization controlling proteins would result in the impairment of the actin polymerization-depolymerization dependent cell movement.

He described the methodology used in the experiment, which had involved time-lapse recording that had begun 30 hours after plating. Images were collected at 15-mins intervals over 960 minutes with a video camera. The cells were manually traced for each frame and migration parameters, including migration path, distance, rate, and directional persistence, then evaluated from the time-lapse films. The migration parameters were next been evaluated using Image J (NIH) and Microsoft Excel.

Migration rates had been calculated as a ratio of the total length of migration paths and the duration of migration. Migration distances were determined as the translocation during a 960-minute period. The directional persistence was calculated as a ratio of the direct distance during a 960-minute period and the total length of the migration paths.

The student’s data from the analysis of random motility of ABI-1 knockout mouse embryonic fibroblasts exhibited impaired, lower movement rates of ABI-1 deprived cells. This was directly related to the observation that their distance of movement was shorter. He had also noted that ABI-1 knockout fibroblasts exhibited stronger directional persistence, suggesting a role of ABI-1 in cell polarization, though it was undetermined. Generally speaking, Morkous concluded, the data had indicated that ABI-1 plays an integral role in the control of actin polymerization-depolymerization that heavily influences cell motility.

The next student presentation of the day was “Cystic Fibrosis: Cystic Fibrosis transmembrane conductance regulator (1R10_B and 1R10_A).” Praise Austin, HCS Class of 2008, and a student at Bronx Academy of Health Careers had done his research on Cystic Fibrosis in summer 2008 under the mentorship of Dr. Yuying Gosser at City College of New York.

Praise first provided an introduction to the disease. Cystic Fibrosis, an autosomal genetic disease that causes early disability and death, is caused by a mutation of the CFTR gene. The CFTR gene (cystic fibrosis transmembrane conductance regulator) controls chlorine transport and can proceed to a deadly phase when the mutation disrupts the exocrine glands and causes build up of mucus in the liver, lungs, pancreas and intestines.

He continued, saying that the CFTR is a member of the ABC (ATP binding cassette group) of proteins and contains two nucleotide-binding domains (NBD), two membrane-spanning domains (MSD) and a regulatory region arranged in the order MSD1-NBD1-R-MSD2-NBD2. The student explained that the most common reason for cystic fibrosis mutation is when CFTR phenylalanine 508 is deleted in one of the protein’s nucleotide binding domains (NBD1).

Cystic Fibrosis, a hereditary genetic disease, affects the endocrine system (sweat glands) and causes the buildup of mucus in the lungs. The CFTR gene responsible for the disorder is a member of the ATP Binding Cassette (ABC) group of transporters, subfamily C and member 7. It is located on 7q31.2 on chromosome 7 (Wainwright et al, 1985). The OMIM (Online Mendelian database) is *602421. The CFTR Gene functions as a chloride transport channel and regulates the functions of other transport channels. Mutations in the CFTR Gene are known to cause Cystic Fibrosis (Mucoviscidosis), which includes symptoms such as liver disease, pancreas insufficiency, pulmonary disease and infertility. Praise stated that research on this gene has been narrowed down to The NBD-1 where the mutation (deletion of phenylalanine 508) is located.

Praise then discussed diagnosis of the disease. CFTR mutations are diagnosed by screening patients through laboratory samples such as saliva, dried blood spots, blood and solid tissue. Based on the amount of CFTR created, the disease's severity can vary. Seventy percent of CF alleles contain phenylalanine 508 and 90% of CF patients contain one copy of this deleted gene. CFTR also contains an ATP binding core with an ABC specific anti-binding beta region and another ABC specific alpha helical domain. The ABC sequences help complete coordination of ATP binding and contain primary determinants of nucleotide binding.

The student explained that, according to data from previous outside research, a hypothesis had been developed that targeted chromosome 7. The CFTR protein had been synthesized from existing alleles that could be used to observe how the reintroduction of the phenylalanine residue would affect a CF patient. The CFTR gene is expressed through e-coli depending on the interaction of the protein with the promoter and regulatory regions. The main mutation in CFTR is the deletion of the phenylalanine protein.

Praise displayed the protein sequence for the CFTR gene NBD-1. The accession code was 1R10_B, which contained 286 amino acids. The crystal structure was determined by vapour diffusion, hanging drop and X-ray diffraction. The pH was 7.5, just above neutral the buffer was sodium acetate, and the temperature was 277 degrees Kelvin scale.

The student concluded by saying that the structure of the NBD-1 in CFTR had been determined through phosphorylating a form of the NBD-1 protein (in order to allow chloride channels to open) and allowing it to crystallize with an unmodified version of the protein.

Anne El-Shafei, HCS Class of 2008, and a student at Forest Hills High School, and Jose Murickan, HCS Class of 2008, and a student at High School for Medical Science, were the next presenters on the program. Their research entitled “Imprints” had been done under the co-mentorship Dr. Thomas Brennan and Dr. John Molina at Bronx Community College in summer 2008. 

In their project, the students had attempted to understand how fingerprinting plays a role in forensics and crime solving. They had begun by studying the AFIS (Automated Fingerprint Identification System), a US government database. The FBI uses fourteen different points of minutiae to digitalize and scan an image into a computer in order to identify a fingerprint. 

All fingerprints are unique, and facilitate reliable and rapid identification. According to Charles Darwin’s cousin, Sir Francis Galton, the odds of two individuals sharing an identical fingerprint are one in sixty-four billion. Formed one hundred days after conception, fingerprints are found in three general patterns: arches, whorls, and loops. Sub-classifications of these general categories include more specific types of fingerprints: plain arch, tented arch, ulnar loop, radial loop, plain whorl, central pocket loop, double loop whorl, and accidental loop whorl. The common types of fingerprints are an arch, loop, double loop, pocked loop, whorl, tent, arch and mixed. The students displayed slide images to illustrate these variations.

The students explained that there are three different types of fingerprints found at crime scenes, including: a visible fingerprint, a plastic fingerprint, and a latent fingerprint. A visible fingerprint can be seen with the naked eye. A plastic fingerprint occurs when a finger comes in contact with a soft surface. A latent fingerprint occurs when the oils, salts and the residue of a fingerprint surface are transferred to another surface. Latent fingerprints are the most commonly found “invisible” fingerprints.

There are various methods of fingerprint search. Different types use a lighting source and enhancement/ visual aid. The newer technologies used for illuminating fingerprints include lasers and UV light, with their fixed waves lengths illuminating oily residue from fingerprints. Another method used to uncover fingerprints causes oily fingerprint secretion to react with a colorless chemical and change color as a result of chemical reaction.

The most common chemicals used to uncover fingerprints are iodine and ninhydrin. When iodine is used, the color becomes brown and when ninhydrin is used, the colorless mixture of oily residue and chemical becomes purple/violet in color. After the chemical reaction is completed, physical methods are then used to enhance the fingerprint. Jose and Anne then showed a short film demonstrating fingerprint analysis.

The students then turned to discussing footprints and shoeprints, which are also important in solving crimes. They can be both three and two-dimensional. The outsole of the shoe has characteristics as a result of damage, use and abuse. Footwear impressions can lead to the identification of a suspect either because of the worn threads on the shoes or a person’s gait. The footwear impressions found at crime scenes can be photographed, lifted or cast to compare to a suspect’s shoes. Anne and Jose then concluded by sharing a second video clip from New York’s Channel 7 Eyewitness News filmed last summer in Dr. Brennan’s forensic science lab, and engaging in a question and answer period.

Rishesh KC next introduced Shirley Mui, HCS Class of 2008, and a student at James Madison whose presentation was entitled “Simulation Technologies and Applications at IST at UCF.” She had been one of a group of the “lucky six” students HCS had been sent to Institute for Simulation and Training at the University of Central Florida in summer 2008 to work under the mentorship of Eileen Smith and Julia Norton.

The student recounted her experience working in the Institute for Simulations and Training (IST) and outlined her exploration of various technologies including: simulation and virtual/mixed reality, teacher training, warehouse, Bodies On/Hands On/Brains On, R.A.P.T.E.R., biofeedback, and V.R.M.C.

After providing a brief introduction on IST, Shirley went into associated terminology. She defined a simulation as a program that imitates a physical process by responding mathematically to data and changing conditions. While there are many different types of simulations, the students primarily worked with the categories of virtual and mixed reality.

Shirley defined virtual reality as a technology that allows a user to interact with a computer-simulated environment. Mixed reality is the merging of real and virtual worlds, producing new environments and visualizations where physical and digital objects co-exist and interact. 

The student then began discussing the various applications. Teacher training simulation involves a user wearing a suit with retro-reflective markers, and six infrared cameras sending and receiving light from the markers. Cameras detect patterns and capture different shapes and shadows, and project images in virtual reality.

The student then went into storyboard, a basic outline that demonstrates what will happen during one’s experience from beginning to end using 3 different types of models. The three models include Bodies On, Hands On, and Brains On. In Bodies On, one’s body interacts with the exhibit, allowing as much user movement as possible. The Hands On exhibit uses the most up-to-date interactive technology to enable the user to do things s/he may not be able to do in reality. The Brains On exhibit allows the user to think about an experience and learn something from it, thereby facilitating the expansion of critical thinking skills.

In terms of mixed reality, Shirley had explored biofeedback, which involves monitoring devices such as the galvanic skin response that measures vital signs such as blood pressure, heart rate, brain waves, skin temperature, muscle tension, and sweat responses. She displayed a photo of a galvanic skin detector that determines the passive-aggressive behavior in an individual through one’s vital signs.

Another mixed reality simulator Shirley discussed was R.A.P.T.E.R. Research in Advanced Performed Technology and Educational Readiness segment of the institute focuses on enhancing human performance, expanding applied research, and developing communication and problem solving through technology. As an example, Shirley spoke driving simulators created to train police officers and truck drivers. Appropriate for drivers education courses, the simulation tests critical knowledge and skills that determined as mandatory by the Federal Commercial Driver License. It blends computer based training technology and simulation.

The final virtual mixed reality simulator the student discussed was that of the V.R.M.C. (Virtual Reality Medical Center in Orlando, Florida), which uses technology to treat anxiety disorders, train military and civilian populations, and to enhance different educational programs geared to medical training.

Shirley concluded by briefly discussing her summer 2009 research in the Department of Chemistry at City College of New York under the mentorship of Professor Michael Green. She is studying the structure and function of potassium (K⁺) ion channels specific to the human nervous system.

After making several more organizational announcements, Dr. Sat introduced the final speaker of the day, Chanel Ligon, HCS Class of 2009, and a student at Bard High School Early College. In a presentation entitled “Myth Busters: Cryptid DNA Analysis,” Chanel spoke about her current research with her mentor, Prof. Todd R. Disotell at NYU in anthropology and bioinformatics.

Chanel introduced her research by discussing the possibility of the existence of such mythic creatures as the infamous Yeti (aka The Abominable Snowman) and Bigfoot (aka Sasquatch). She stated that people around the globe claim that these legendary creatures are elusive and shy, seeming to always avoid human contact. About 450-500 sightings are reported each year in America and 150-200 in Canada. Flesh, blood, hair, and tissue samples are found and claimed as belonging to Cryptids. From these sources DNA is derived and can therefore provide conclusive proof as to the actual identity of these unknown creatures.

The student then spoke briefly about her mentor, Prof. Disotell. A professor at NYU with a PhD in anthropology, he examines potential DNA samples of the Yeti and Bigfoot in order to debunk these legends and myths.

Chanel then went into cryptid DNA analysis. Cryptids are animals that might possibly exist in nature but whose existence have not yet been accepted by modern science. Extracting DNA from samples found worldwide, scientists can exactly match them to identified species or possibly new species, or potentially to a relative of the unknown species. Analysis of mitochondrial DNA is the most accurate method of identifying a species in these instances.

The student then described the procedure for the analysis. First, the DNA found in the samples from unidentified species is amplified, creating billions of copies. The DNA is then sequenced by strand separation (A from T, C from G). Scientists later determine the exact sequence and compare it to a database of all known living species.

Chanel went into problems encountered in the identification process. For example, a major problem had been encountered with the DNA of a Northern Ontario “Sasquatch.” There was no DNA actually found in the samples, and it had been determined that either the DNA had been destroyed by weather or natural organisms, or the samples had simply not been biological at all. This pointed to the likelihood of the creature’s non-existence.

With respect to programming used for analysis, Chanel had used Python script (a high level programming language) to compare the DNA sequence of the Cryptid known as Bigfoot to the DNA sequence of a chimp. With Prof. Disotell, she had created a program that took the DNA sequence of Bigfoot and compared it to the chimpanzee's DNA sequence to observe the similarities.

Chanel turned to discussing another case, the Kentucky Bigfoot. A plate with food had been set outdoors as a lure and trap for Bigfoot. Mitochondrial DNA testing of residue on the plate (using programming similar to Python) had revealed that the creature was not actually Bigfoot but actually a human of German origin.

Chanel continued, saying Prof. Disotell has already debunked numerous similar cases and has yet to find evidence using mitochondrial DNA of Cryptid existence. So-called DNA evidence presented to Prof. Disotell for analysis has, to date, ended up merely being that of other common animals or humans.

The student concluded her presentation by discussing the significance of this analysis in the scientific community. Using mitochondrial DNA to identify unknown species is important, because in the future it may actually result in the identification of legitimate new ones that may be added to the world's scientific database of all known living species. Second, debunking such legends can also be beneficial to the scientific community because it can diminish time and money wasted on further study of so-called mythical creatures rather than actual identified species. Chanel ended her presentation with a question and answer period.

Thus concluded the third seminar of the HCS 2009 summer program, and the meeting was adjourned.

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