Team:TelHai-Migal Israel/Human Practices

Feedbacks from professionals

Dr. Lior Nissim

Dr. Lior Nissim is Head of the Synthetic Biology Laboratory at the Hebrew University of Jerusalem.

Our project builds upon the work of Dr. Lior Nissim and is based on collaboration between Dr. Lior Nissim, Prof. Gidi Gross and Dr. Hadas Weinstein-Marom, which led to an innovative new approach to solving the leakiness problem and the safest way to insert our gene of interest. Dr. Weinstein-Marom and Dr. Nissim have met numerous times to discuss the project and how to build the experimental systems. After planning and building our genetic sequences, we received Dr. Nissim's feedback and modified the designed sequences. Thus, in fact, we developed two sets of modules to be tested during our laboratory experiments.

When asked for his opinion about the safety of our project, Dr. Nissim replied – "Although the insertion of the genes, in a future clinical application, would occur through viral vectors, the method is considered very safe and specific. Because the model is designed so that only activation of both promoters will lead to the translation of proteins." There is no dependency on inhibition at the mRNA level, as in the original system and hence, there is no fear of a basal level expression. The special mechanism of trans-splicing makes our system safer than anything published till today.”

Prof. Tamar Yablonski-Peretz and Dr. Albert Grinshpun

We contacted Prof. Tamar Yablonski-Peretz - Head of the Sharett Institute of Oncology, and Dr. Albert Grinshpun Albert - attending physician in the Radiotherapy Unit, Dept. of Oncology, both at Hadassah University Hospital in Ein Kerem, Jerusalem, in order to discuss possible applications of our gene therapy tool for cancer treatment.

Apart from our idea of inserting genes into specific target cells within the patient’s body (in-vivo), Prof. Peretz and Dr. Grinshpun suggested the possibility of using our system as a means to create immunogens from tumor biopsies outside of the patient’s body (ex-vivo), thus refraining from using a virus to infect the entire body. The meeting ended with a prospect for a future collaboration and continued counseling on their part.

Dr. Itamar Yadid

Dr. Itamar Yadid is Head of the Microbial Metabolic Pathways Research Laboratory at MIGAL - Galilee Research Institute. We met with Dr. Yadid for his feedback on our project.

“The Logic AND Gate device is a product of electrical engineering and can execute a Boolean function by recognizing two binary inputs and producing a single binary output. However, this mechanism cannot be implemented in biological devices due to the variety of inputs that these devices can receive. Furthermore, in biology, such a binary signal is nearly impossible because a true 0 signal is not defined. The process of mRNA trans-splicing rarely occurs in animal cells and an applicable method must be identified to ensure that the process occurs in all the cells. The system suggested is good, though somewhat complicated. There are simpler devices such as split-protein reassembly, also called protein fragment complementation. This device relies on the appropriate fragmentation of protein reporters, such as the green fluorescent protein or firefly luciferase, which, when attached to possible interacting partners can reassemble and regain function, thereby confirming the partnership. On one hand, the Logic AND Gate system is too complicated; however, on the other hand it is more sensitive and accurate. Checking the production of the complete mRNA should be done with the PCR and not by FACS because it is more rational and accurate. It should be taken into consideration that the mRNA in some situations could lead to the production of new proteins that may be harmful to the cell. In conclusion, the Logic AND Gate system is interesting and elegant even though it is sophisticated. I suggest doing reverse transcriptase PCR to detect trans-spliced RNA.”

Events


Connecting with patients Interview with Tracy
Cart of hearts Hair donation drive Cancer Awareness Day

Interview with Tracy

Interview with Tracy Piada

To better understand what the patients go through, in addition to visiting the Oncology Department we wanted to have an in-depth conversation with someone who was going through treatment. Tracy Piada is a lovely, inspiring woman, who is currently coping with breast cancer yet remains strong and optimistic.

During the interview Tracy described how she had received the news of her diagnosis and the side effects she had experienced throughout treatment, such as debilitating fatigue and hair loss. Tracy added that it was harder for her family to accept her hair loss, but even so she decided not to wear a wig, because she did not want to hide her illness. However, she told us of her good friend who also suffered from breast cancer and without the wig she did not feel comfortable leaving the house or going to work. At the end of the interview she emphasized how important it is to undergo regular checks for early diagnosis.

Link to video

Connecting with patients

Visiting the Oncology Department at Ziv Hospital in Zefat

We visited the Oncology Department at Ziv Hospital in Zefat in order to connect with the community that we are trying to help though our project. The goal of the visit was to learn about their difficulties, listen to their stories and understand what they are going through.

During our visit, we met with chemotherapy patients and their families before and during their treatments. We handed out popsicles, sat with them, and helped them pass the time during their treatments.

They shared with us the difficult side effects that they experience during and after each treatment. The most common side effects mentioned were extreme fatigue, loss of appetite and hair loss from their entire bodies, including their eyebrows.

After seeing how bored the patients were during their treatments, we thought about what we could do to help them pass the time. Therefore we donated a wooden book cart filled with different books and magazines that were collected from the community.

Cancer Awareness Day

Although cancer is in our awareness, people still prefer to forget about it

After interviewing Tracy, we noticed her saying that when people heard that she was diagnosed with cancer and receiving treatment, it made them more aware of the risk and encouraged them to be checked. Although we all know about cancer, people still prefer to ignore the risk and think that it would not happen to them.

Cancer Awareness Day occurred on the 4th of February, and we thought it would be a great opportunity to remind people in our local community of Kiryat Shmona how important it is to be checked and to be aware for one's own body and health.

In order to catch people's attention, we prepared chocolate cookies to which we attached notes containing information such as what is the most common cancer in men or women, various statistics and much more. We shared the chocolate cookies in the central mall of Kiryat Shmona to remind people that this is no longer something to be ignored.

Cart of hearts

When we first visited the Oncology Department of Ziv Hospital, we noticed that patients must wait a very long time for the oncologist and for the chemotherapy session to be over. Sometimes they are accompanied by family members or friends to help them pass the time and sometimes they are alone. We decided to bring them a library full of books so that even if they come alone, they will not really be alone, and will have something to do. As we designed the library, we wanted to make sure they would not have to get up during chemotherapy, so we decided on making it a cart. It was important for us that it will be on wheels so staff could roll the cart between the patients. The book cart was prepared with great love, by a local carpenter, Shlomi, from Etz Hagefen woodwork who did it completely voluntarily for our important cause. He coped with all our requirements and did an amazing job. We then turned to the community to collect second-hand books and got a heart-warming response. We collected books in a mix of languages and genres. For weeks we collected books from the community and created an impressive wide-ranging library. After weeks of work, we returned to the oncology department to give them our gift, and some delicious popsicles. We were delighted to see that the gift was received with great joy and love.

We are hoping that we helped in our own small way and that this cart will make it a little easier during the long waiting times.

Hair donation drive

While meeting cancer patients and their families during their chemotherapy treatments, they shared with us their struggles and their difficulties that are caused by the side effects of cancer treatments such as hair loss. After meeting the patients, we felt that visiting them was not enough; we decided to embark on a journey to help them and connect their needs to the community resources by carrying out a hair donation drive in support of cancer patients, an event to occur for the first time in the northern peripheral area of Israel. We contacted the charity called Zichron Menachem, an organization whose goal is to create wigs for every cancer patient in Israel who needs one or wants one.

We hoped to engage the public, share with them what we experienced and learned, and give them the opportunity to be part of a significant contribution to the cancer patients’ community. Our town rose to the occasion and were more than happy to participate in the event and donate hair to cancer patients. As part of the event there were food stands, live music and educational activities for children.

We also took it upon ourselves to invite the mayor of Kiryat Shmona, Mr. Avihay Shtern, who gladly attended the event and ceremonially cut one of the braids himself. The event was published in the newspapers and, most importantly, we collected over 30 braids to donate. These braids were used to make wigs, which were personally customized to each patient matching their original hair color and style.

Each person who donated their 12 inches of hair received a certificate of gratitude from our team and the Zichron Menachem charity.

Link to video

Ethics


As part of our work, we felt it was important to understand fully the subject of ethics in general and particularly in our study; what questions may arise from the research and what should be emphasized. To that end, we approached Dr. Eli Pitcovski, a philosopher and lecturer of philosophy at Tel-Hai College, and Drs. Shlomo Shapira and Andrea Szuchman-Sapir, members of the Ethics Committee at Tel-Hai College.

During our conversations with them, we realized that all ethics issues must be clear and resolved at every step of the research, even before starting the actual wet work, as each can raise different ethical questions. Once human subjects or human material are involved in the study, any act or any piece of information we obtain requires approval of the Committee. In our study, we only use a human cell line; therefore, in this respect there is no need for an ethical approval to conduct the experiments.

From the philosophical point of view, some of the ethical issues we may encounter are whether there could be an ill conduct of this tool and whether healthy individuals may suffer any harm upon should some parts of the therapeutic system we are developing are modified. Currently, our system is carefully designed to avoid any possibility of harming a healthy person, or healthy cells in cancer patients; it is possible, however, that in the future the system would be modified so that some healthy cells are also affected. This is the greatest fear of synthetic biology. We do not know what the long-term impact would be, in both health and social terms. Would we see no diversity in the future, because people will be able to engineer themselves according to the most up-to-date fashion? Can the trait that we attempt to eliminate be the one that would save us from an epidemic in the future? Or maybe, if a certain feature does not fade away, it is because it serves us in another way?

mistake made would leave a crucial mark and determine the future of this field and of us who pursue it.

Practically and philosophically, in terms of developing a research, we have learned many new and important concepts and lines of thought in the field of ethics, which have contributed to our knowledge as well as to the way we view our research.