SEP's CIRM SPARK interns reflect on their summer 2018 experience.

9/14/2018

BRENDA

This summer has been one of the greatest experiences I have had so far thanks to the CIRM internship program. I have learned so much about stem cells and how they become other cells. This summer I specifically focused on the development of T cells from stem cells and how those T cells become different variants of themselves. For example a naive T cell, meaning a T cell without a defined purpose, has the possibility to become a Th1 or a Th2 cell. Although these two names seem similar, they target completely different pathogens or in other words a particle that is harmful to the body. Th1 on one hand focusses on storing information of infections of the past in its memory and when that pathogen arrives again in the body the Th1 uses that stored memory to tell other cells how to react. On the other hand, Th2 cells focus mainly on the body’s immediate defense to bacteria or other pathogens. It only acts in the moment, unlike the patient Th1 cell.

What I also learned about this summer is a structure I never heard about before within RNA. This structure is called MicroRNA, and its purpose is to downregulate, lower, the production of protein with a cell. This summer I was focusing on which genes are affected by microRNA, specifically on MicroRNA 29, because it has been shown to have effects on T cell development and it affects what path the T cell will grow into.

Overall this summer has been one of the greatest I have ever had because I got to learn so much about the immune system and how stem cells play a role in that process. And I also learned the amazing structure that is Micro RNA and it purpose. Having learned so much during the summer I am grateful to have had this experience and to learn so much from it.

GENNIFER

When I was seven, I remember looking up at the stars, I stared hard at the moon through my car window, thinking that it only revolves around me as it followed me home. I later learned in class that we rotate around the sun, as gravity holds the spinning planets in place, simultaneously, the moon revolves around the earth. Out of nowhere, I abruptly felt an actual light bulb switched on above my head once I learned how day and night came. Overcome with curiosity,“ Where did the Big Bang take place? When will my Big Bang happen?”

My interest dissipated as I entered into my high school career. I was struck with incoherence, an inconsistency to my thoughts, as I leaned my shoulder against the wall—for I had already decided to let my fatigue to take over. I felt lacking, unconfident in my abilities even to solve a simple balance chemical equation in chemistry class. Science was not my forte. I could never see myself working in a lab setting.

Still, a spark within me still held onto that childhood curiosity of mine. I remember sitting on the bus on my way to school reading about stem cells, which were fascinating to me. We can use these little cells for so many scientific research.

My Big Bang unfolded when I was accepted into the UCSF SEP internship program. I
studied the human-specific population of cortical neural stem cells and evaluated the signaling mechanisms that govern the formation of their identity. Through my performance, I am also contributing to this phenomenal study, helping my community by potentially providing information to help cure mental illnesses. At times, the results of our data did not come out as we wanted it to be. The staining went wrong, and the images were lacking. I would have to repeat the experiment or troubleshoot on the spot continually. However, it's all a learning process. Even if I do get beautiful image stainings, I still need to repeat the experiments to confirm my results.

Learning was not the only side that is needed under this program. CIRM encouraged us to share our internship experiences on social media. I posted once a week on my studies, what I’ve learned, and how I could teach my viewers about this new research I am performing. I remember in one of the first few meetings we had, where we had to share our research with our peers, “ I can actually understand your studies,” a friend of mine claimed.

I felt powerful, in a sense, that I was able to communicate my knowledge to others to help them understand and teach my study. When I talk to my family and friends about my summer, I feel confident in my ability to comprehend these complex ideas. I could see myself researching, engineering, and fighting for a solution. I want to find the best form of gene therapy, and map each neuron of the brain. Through this two month program, science has become a new passion for me, a cornerstone of my new academic pursuits. It strengthened my theoretical knowledge and gave me an experience where I witnessed the real world laboratory setting. Not only did I learn the fundamental techniques of immunohistochemistry and microscopy, but I was able to receive encouraging advice from the scientists in the Kriegsteins lab and especially my mentor, Madeline Andrews. The experience in a lab comforted me by the idea of the never-ending changes that lured me to a world of thought and endless potential.

JACKIE

This summer has been an interesting one. Having the opportunity to study in a world-renowned school like UCSF is big for me. None of my family went to college. It makes me feel as if I’m on the right path. Working in the lab was just as much fun as it was struggle and frustration. During the experience, I did love learning about different subjects of science but I don’t think I could work in a lab for the rest of my life. This experience is something I’m grateful for because I got to not only be here but discovered more about the science career pathway. I’ve also learned a bit more about myself as well. I discovered that I do have a lot of self-doubt along with the fact that I hate not being able to be good at something immediately. It taught me patience. I had a lot of identity crisis while I was here. I’m a half black half samoan woman at UCSF. I don’t see a lot of black folks here. I definitely don’t see any polynesian people here. However, I’m here and there is no reason why I shouldn’t be.

JASON

Over the course of eight weeks I researched how stem cells know when to be active or when to be dormant. For those who are unsure, stem cells are cells that lead to the development of all other cells in the body. They are formed shortly after sperm meets egg, and they play a pivotal role in the growth we see children go through. Even as a fully developed adult, stem cells are still present in one’s body, albeit at much lower levels than a growing child. Even though stem cells aren’t completely lost when one fully matures, their numbers dwindle. It is as an adult that stem cells grown in a lab may be tasked with healing, where their powers when one was growing can be manipulated in a way that allows for a new way of healing. Instead of relying on chemicals to alter reactions in our bodies or physically going in and surgically removing a part of one’s body, the aim of regenerative medicine is to allow the body to theoretically “regrow parts”. This is especially crucial for conditions we currently have no effective way of curing without long periods of time or excessive damage to the rest of the body, such as cancer or trauma. This is achieved by harnessing the powers of stem cells in regenerating any type of cell imaginable, replacing anything from malignant tumors to vast stretches of skin destroyed by third degree burns. However, stem cell therapy remains a largely inaccessible, unpractical, expensive procedure. A reason for this is the short shelf life of stem cells while in storage. That is where my research comes in. I spent the summer looking at a reaction called acetylation, which I have concluded to be more prevalent in areas of muscle that are close to an injury. Since an injury causes the little stem cells in adults to be activated, I made the connection that acetylation is linked to activation of muscle stem cells. From this, a future project may be dedicated to seeing what happens if acetylation is inhibited or stopped, and if that will allow for long term storage of stem cells grown in the lab for use in patients who need them. This research goes beyond muscle. This research can lead to other discoveries in stem cells’ activities in other areas of the body, where similar reactions may be signs of activation. Eventually, this research may lead to a method of tracking or even preventing the process of stem cell activation, so that it may be active when it needs to be, in a patient’s body, not a storage container.

JOSUE

What is sectioning, microscopy or immunostaining? Once introduced to the lab, these big words were commonly used without me understanding their purpose or function. Yet I didn’t fear those words because I knew that I would have the opportunity to learn all those different techniques during my 8 week stay at UCSF. The first weeks were slow, but I learned about the liver anatomy and regenerative process. Things like Wnt signaling, βcatenin, and Axin2+ were introduced. I gradually understood how hepatocytes respond to the different signals when the liver was injured. Also, through lab meetings I was able to understand that each hepatocyte is categorized in subgroups due to its location and protein production. Learning more about these cells excited me and helped me understand that these cells have unique stem cell properties. Eventually I was introduced to the microtome which is a machine used to slice small strips of tissues. When I first saw my mentor use it I thought it was strange how he had to breath on the paraffin block to give it adequate moisture. Making continuous sections of tissue was annoying because every time I would rotate the machine the delicate strips would break or fold which wouldn’t be useful for seeing under the microscope. My hands got wet, sticky and sweaty even though I worked extremely slow and careful. Later, immunostaining involved adding clear liquids onto the slide. This process was extremely long because I had to continuously add liquids every 5 minutes and as well antibodies that had to be incubated for an hour. Though sometimes I found it fun sucking up the liquid material that no longer was needed on the slides when its incubation period ended. Lastly, I learned how to use the microscope to visualize the staining, which looks complicated but was easy to learn. I really enjoyed seeing the beautiful fluorescent designs and cell structure under the microscope. Most of my time here at UCSF involved me learning how to do many things in the lab. That meant that I began my official project 2 weeks before the end of the program. Lately I have been really stressed with making an abstract, 10-minute presentation and poster. Although throughout my time here I plan to not give in to the pressure and present any data despite it not being what I wanted to share. UCSF did not only challenge me, but it opened me to a new environment, the research field. I am glad that I had the opportunity to work with mice, give presentations and do work on my own. Overall, I am thankful for the opportunity to work with professional scientist who have positively influenced my personality and future path.

LUIS

During this summer I had the opportunity to work with research scientists that were focussed on the eye field. I had a great mentor who helped me to carry out my project. The project I was given is part of my main mentor´s research. My project was to investigate similarities between a native mouse retina and a mouse retina organoid. I was able to dissect a mouse eye to isolate retinal tissue that was later placed in a plastic mold to embed and freeze it in a solution of OCT and sucrose. Another technique I learned was cryosection, where I tested my patience and cryosection skills. Each section was immunolabeled with different cell markers to look at them under the microscope and conclude whether there were cells or not. We took the coolest pictures I have ever seen in a laboratory of those immunolabeled sections. My mentor shared with me that my project helped her to know how well-structured her organoids were. Before I was accepted to this program and had all these experiences, my thoughts about being a scientist were a little negative. I had never thought that I would have an opportunity like this one and take advantage of it. I discovered what I am capable to do, raising up all my expectations and motivation. One challenge I had through the program was the language. My knowledge with the English language is just enough to communicate in simple situations. However, I had the support of my mentor who worked harder to make sure I understand and to learn as much as possible. This experience, made me reconsider the possibility of being a scientist and with that, being one more person who would contribute to the development of tools to improve the life of people.

MAEVE

When I was accepted into the SEP program I don’t think anything I could’ve conjured in my mind would compare to the experience I had. I personally didn’t struggle with understanding the concepts that my mentors had taught me. What I did struggle with in the beginning was the practice of those experiments and the environment of a lab. Luckily SEP, my mentors and my fellow interns were the kindest individuals I have ever encountered.

The first couple of weeks were hard for me because I was starting my experiments and in the very beginning I made, what I felt to be, a catastrophic mistake in which I stained all 36 of my coverslips incorrectly. I was devastated and I felt like a failure, because I knew my internship was only eight weeks and, “since I already screwed up the first experiment what does that mean for my future experiments?” was what I thought to myself. However my mentors were very supportive and gave me time to grieve what I felt to be not only a waste of resources but also a waste of everyone’s time. Additionally I spoke with fellow interns who had similar hiccups in their experiments. Through that experience I was able to work on my communication skills, specifically communicating when I was having a hard time and needed support. This experience was very educational which gave me awesome insight into my future. Thank you CIRM!

SOFIA

When I first entered this program I was nervous and scared. Nervous and scared because I didn't know what to expect; science isn't something that I understood so when I started, the first thought that came in my head was will I be able to actually do this? The first couple of weeks I was unsure but then I learned how to stain cells and that caught my attention. The process of staining could be sometimes confusing for me but I understood how it worked. It was fun to stain cells and see them under the microscope. I did everything from staining stem cells to taking data from them. What I did to help me understand what I was doing was to break down every piece of information that I was learning into my own words. I mentally annotated everything and tried my very best to know what I was doing. I'm glad that this summer I got to work in a lab and actually experience science one on one. I got to learn a lot of information that I can share with people that struggle with science like how I do. This was an amazing opportunity for me to take especially since science and I have had a rocky path. This internship made me have a clearer view of what I want to do, maybe not working studying cells but working on how to make replicas of organs using stem cells. My mom was very proud to know that I tried something related to science and she’s excited to see where this exposure will take me. I am too thinking about what to do next. I feel like personally I want to know what other science jobs are out there and just be more open-minded to the science field. My thoughts of science progressed even though sometimes it can be a struggle but like mentor Annarita said, “Science is a long process but when you when get closer to the never ending answer it feels rewarding”, and sure enough I feel like I’ve been rewarded.

VY

Arid1a is a subunit of a chromatin remodeling complex called BAF, which allows genes to be turned on or off throughout development by allowing DNA turn into RNA (it’s a single strand of DNA that can turn into protein). Humans with mutations in ARID1A develop Coffin-Siris Syndrome (CSS) and intellectual disability. We developed a mouse model for CSS using a conditional heterozygous knockout in cells expressing Nestin using a Cre-Lox approach (all cells of the central nervous system lose one copy of Arid1a). In the Nestin-Cre;Arid1a f/+ knockout, neurons (nerve cell that receive a signal to processes and transmits information through electrical and chemical) populate the cortex (the outer layer of the cerebrum of brain that is important for thinking) in higher density compared to controls. In order to monitor open and close stage of chromatin (a process in cells that turn DNA to RNA, and RNA to protein), we inject into the mice’s mother a chemical called Bromodeoxyuridine (BrdU) at e13.

The cell will incorporate BrdU as thymidine (thymidine linked to deoxyribose and occurs as a structural part of DNA) because it is a thymidine analog, and it will be taken up during the DNA synthesis phase of the cell cycle. This helps us to mark the cells that produce at E13. Injecting BrudU help us to observe the cells that are proliferating. When the mouse is at P21 we take their brain and study it using immunofluorescence staining (mark specific cells with specific neuron markers). We investigated if the proliferative cells are excitatory or inhibitory. Based on the result we have for BrdU, Chet produced lesser daughter cells than the control. Also, Chet have lesser inhibitory cells than the control when we did quantification in the upper layers. This difference might have cause the brain to function differently.

Before this summer I barely knew anything about stem cells, but now I understand that in my lab we use BrdU to mark, among all other cells types, proliferating stem cells. From there I learned that stem cells can choose to proliferate into more stem cells or can choose to turn into specific types of cells in the body. In the brain, stem cells work in a similar way. Through this summer I learned so much more about biology. I love to go to lab every day because I know I will learn and observe more about sciences. The hardest challenge for me in this lab is to know and understand about biology, especially about cells. But thank you so much to my mentors, who were always next to me and very patient to guide me to a right path. After this summer I’m getting very excited with doing research in future. I hope to have more opportunities like this in future.

WENTAO

Today I will share about my experience working in the scientific lab. First, I joined in the internship program with the Science & Health Education Partnership (SEP). In this program, I have the opportunity to work in the lab. On the first day I studied some knowledge about the lab safety. This training is important, because it told us about how we work safely in the lab. After that I really worked in my lab. The first day in the lab, I was very shy because I just know my mentor. I even do not know where I can sit. But my mentor was a very friendly and funny guy. So I felt relaxed working with him.

Our lab worked on modeling lung disease using airway stem cells; lung disease meaning people who have the breathing problem. However, airway stem cells come from between the trachea and lung, that small part, and they are difficult to get from patients because it requires an invasive procedure. The invasive procedure is very dangerous, and we just get a few cells. We are trying to find alternative ways of obtaining airway stem cells for modeling airway disease. We are trying to use transcription factors to convert skin cells into airway stem cells. Transcription factors are proteins that turn on or off other genes in a cell. My focus was to clone human and mouse airway transcription factors using PCR. PCR is a session that uses a thermocycler to copy more pieces of DNA. We got the PCR products for 12 out of 14 transcription factors and cloned them. After we got the results from PCR product and cloning, and we put those transcription factors into the plasmid and cultured. We performed a restriction digest to check the size by using the enzyme called “EcoRI”. For this step, the enzyme will cut off the factor and we will move to the vector. Then we sent the DNA to be sequence and checked if the sequence was correct or not. Those were steps I did in the lab. Also my mentor was told me about the future: “In the future, we can use this cell to understand the causes of common breathing problems, and it may lead the treatment.”

In this program I am not just working in the lab, I can get support for writing personal insight questions. Also I can learn some skills to give the scientific talk and make a big poster. By the way I go to visit UC Santa Cruz, that college is very beautiful and large. The tour introduced about majors that the college has and how to apply to UC. Finally these experiences I think are very helpful, because it helps me to prepare for the future.

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