Welcome to the B(E)log! Here you can find posts about BMES, the BE department, or Bioengineering in general.

B(E)log Posts are Back!

Ryann Joseph, BMES Board

BMES is happy to announce that the B(E)log posts have been brought back by the 2023 BMES Board, with more content coming and to come. Below are three articles about bioengineering happening in our world and our takes on this as BE students. The members of the internal committee have been working hard to make content to review.

Genetically Engineered Mice Models Infected with COVID-19

Jonathan Largoza, BMES Board

One of the most common methods researchers employ to understand human diseases and develop novel therapies is through genetically engineered mouse models (GEMMs). However, infecting mice through certain human diseases with the same effects can be challenging.

One of the most pressing issues over the past few years has been the Coronavirus pandemic. Scientists have failed to create a GEMM with Covid-19 until now. Researchers at the NYU Grossman School of Medicine have successfully genetically modified mice to get a human form of Covid-19. These mice even experience the same symptoms and the same immune cells are activated as a human infected with Covid (as opposed to previously dying immediately following infection).

These mice were made with the gene instructing the creation of ACE2-a protein linked to Covid-19 and its ability to attach onto human cells. Previously, techniques like CRISPR could only edit a few letters of genetic code at one time; however, this study required the modification of genetic code that was 2 million letters long (to the point where it was more efficient to start from scratch).

Senior study author, Jef Boeke, and his lab developed a genome editing process for yeast and then applied their yeast technique to gene modification in mammals (including switches that turn on different genes). Then, yeast cells were used to assemble DNA sequences up to 200,000 letters long at one time, which were then placed (via a delivery method called mSwAP-in) in mouse embryonic stem cells, solving the issue of inefficient and slow gene editing. mSwAP-in was used to create a humanized mouse model infected with Covid-19 by swapping in 180 bilobases of the ACE2 gene. Specifically, this method cut into a key location of DNA code surrounding the gene and swapped the synthetic code in with a “quality control mechanism” that allowed only cells with the synthetic gene to survive.

Through m-SwAP In, humans now have the first animal model that mimics Covid-19. Thousands of mouse lines already exist since GEMMs have been used for quite a while, so it will be easy for scientists to crossbreed mice for ACE2 expression. Even better, we can now observe the effects of Covid on the body combined with other diseases or conditions (that make the virus even more deadly) like diabetes or even regular aging. This new GEMM can offer insights previously hidden to researchers about a deadly virus that took a drastic toll on the world. Boeke even says that this has been the major missing piece in developing new drugs against Coronavirus.

Link to papers:

Mouse genome rewriting and tailoring of three important disease loci

First mice engineered to survive COVID-19 like young, healthy humans

Genetically Modifying Individual Cells in Animals

Makayla Cheng, BMES Board

Researchers at ETH Zurich have developed an innovative method utilizing CRISPR-Cas gene editing to genetically modify individual cells differently within animals, enabling the study of complex genetic disorders in a single experiment. Traditionally, investigating the genetic causes of diseases involves knocking out a single gene and observing the consequences, but this becomes challenging when multiple genes contribute to the pathology. The new approach involves simultaneously making dozens of gene changes in the cells of a single animal, akin to creating a genetic mosaic. While each cell only undergoes alteration in one gene, the various cells within an organ are modified differently, allowing for precise analysis of individual cells and the study of the consequences of multiple gene changes in a single experiment.

This groundbreaking method has been successfully applied for the first time in living animals, specifically adult mice, as reported in the latest issue of Nature by a team led by Randall Platt, a Professor of Biological Engineering at ETH Zurich. Using the CRISPR-Cas gene editing technology, the researchers employed adeno-associated viruses (AAVs) to deliver instructions for gene destruction in the mice’s cells, targeting the brain in this study. The scientists focused on 29 genes associated with the 22q11.2 deletion syndrome, a rare genetic disorder in humans with diverse symptoms often misdiagnosed as conditions like schizophrenia and autism spectrum disorder.

The study revealed three genes responsible for dysfunction in brain cells, providing new insights into the disorder. One of these genes was already known, while the other two had not been previously studied extensively. The researchers believe that understanding genes with abnormal activity in diseases can aid in developing drugs to compensate for these abnormalities. The method is applicable to studying various genetic disorders, especially those involving multiple genes, such as congenital diseases and mental illnesses like schizophrenia.

The researchers have applied for a patent on this technology, with plans to use it in a spin-off venture. This approach offers advantages, including the ability to analyze living organisms and inject AAVs into animals’ bloodstreams to target different organs. Additionally, the study highlights the potential to reduce the number of animal experiments through advancements in CRISPR perturbation techniques that perturb the genome in a mosaic-like manner. Another recent study from ETH Zurich demonstrated the application of CRISPR perturbation in organoids, miniature organ-like structures grown from stem cells, providing further avenues to gain insights with fewer experiments and potentially decreasing reliance on animal research methods.

Link to paper:

Genetically modifying individual cells in animals

Antibody Drug Conjugates and Their Role in Fighting Cancer

Krish Modi, BMES Board

Over the past years, the advancement of ADCs has been sweeping the biotech/pharmaceutical industry. ADCs (Antibody Drug Conjugates) are a novel form of chemotherapy that are able to specifically target cancerous cells. They represent the cutting-edge of pharmaceutical development and have the potential to change how cancer is treated.

ADCs are made up of three main parts: a monoclonal antibody, a linker molecule, and a cytotoxic payload. The monoclonal antibody performs its job by selectively attacking cancer cells while keeping healthy cells unharmed. The antibody attaches to the cancer cell by using the linker molecule as a connector. Then, the cytotoxic payload, a potent medicine, is released directly to the cancerous cell. 

This precision-guided approach differs significantly from traditional chemotherapy. Cancer cells grow exceedingly fast. Traditional chemotherapy takes advantage of this and targets fast growing cells. However, there are also many other healthy cells in the human body that divide at a high rate such as hair and gut cells. For this reason, side effects of chemotherapy typically include hair loss, nausea, and vomiting. Overall, these side effects can significantly diminish cancer patients’ quality of life. 

What makes ADCs so exciting is their potential to overcome some of the limitations of conventional chemotherapy. By targeting specific cells, ADCs are able to eradicate tumor cells while not affecting healthy cells. They have shown outstanding success with previously difficult cancers including leukemia, lymphoma, and breast cancer. Additionally, ADCs are being investigated for use in other medical fields including autoimmune disorders and infectious illnesses. This ability to adapt enables the possibility to develop novel therapies for a range of diseases.

Looking ahead, ADCs will have a long-term impact on medicine/biotechnology. They mark an important development in personalized medicine, which allows for the customization of treatments based on each patient’s unique cancer profile. Not only does this enhance the efficacy of the medication, but it also reduces the potential of treatment resistance.

One-by-one, pharmaceutical companies are furthering their development of ADCs as all signs point to it as the future of medicine. These companies are actively funding ADC R&D, via internal initiatives or joint ventures with specialist firms. The industry’s desire to provide patients with more effective drugs is reflected in this recent move toward ADCs. The commercial success of ADCs like Trastuzumab Deruxtecan (Enhertu) and Moxetumomab Pasudotox (Lumoxiti) are signs of this. They have not only proven the clinical promise of these medications but also established optimism about the pharmaceutical industry’s ability to develop cutting-edge treatments. 

New Ways to Screen for Embryotoxicity

BMES Board

Many expectant mothers face difficulty in understanding how the medications that they take impact their baby. Even doctors don’t exactly know which drugs to prescribe to pregnant women because they don’t know how toxic it could be to the embryo and how it could affect the development of the embryo. One particular area of concern is the heart because it is the first organ to develop in the womb.

Researchers at Syracuse University’s System Tissue Engineering and Morphogenesis (STEM) lab have created a possible solution to this problem by experimenting with human induced pluripotent stem cells to study tissue regeneration, regenerative medicine and stem cell engineering. Professor Zhen Ma and his team developed a process to use cell patterning and stem cell technology to make a 3D tissue model to mimic early stage human heart development.

They started with polymer that has tiny patterns in it which the stem cells attach to. The cells eventually become a three-dimensional structure with tissues. This new technique allows cells and tissue to form during cell differentiation which can form more layers and accurately represent how tissue grows in humans naturally.

This also provides a new alternative to testing different kinds of drugs as the cell lines are human based, so it is much easier to determine the effects of drugs as opposed to the usual which is animal models. The process also allows for the development of other kinds of tissues and not just cardiac tissue. Because of the use of stem cells, medications could be tailored specifically to an individual which would be very useful for testing a variety of drugs.

Link to paper:

Generation of spatial-patterned early-developing cardiac organoids using human pluripotent stem cells

 BE Department Interviews: Caroline Atkinson

BMES Board

Last week we had the opportunity to sit down with an extremely promising junior in the bioengineering department: Caroline Atkinson.  At Penn, she is involved in Engineers in Medicine, Alpha Phi Omega, West Philly tutoring club, and is a member of the club squash team.  In her free time, she enjoys playing guitar and performing at open mics and fundraiser events.

As a bioengineer, her plans for the future include going into industry and perhaps working at a medical device company.  She is interested in the business side of industry as well as the engineering side.  Caroline explained that minoring in Engineering Entrepreneurship has given her exposure to the business of biotech and healthcare cases.  Some of the experiences that she has had include research in a lab and an internship at LifeSensors.

In her lab, she has mainly worked on building a neural microscope and designing and 3D printing with Solidworks. At her internship with LifeSensors, she worked mainly with protein purification which she described as a direct application of BE 220.
One of her favorite parts about being a bioengineer at Penn is the opportunity to take classes such as BE 309 which allow her to “see the concepts you learn about in class applied in real life.” A piece of advice which she wishes she knew as a freshman would be to try out more clubs and expand upon your interests more than high school because Penn has so much to offer. An example of this for her is participating in club squash. It allows her to destress while relaxing and enjoying the sport but at the same time teaching her valuable time management skills.

On a more serious note, like many Penn students, Caroline admits that at times she has dealt with imposter syndrome. However, she says that she learned to cope with it by being honest with people and understanding that imposter syndrome is something almost everyone goes through. Some advice that she has for others about this subject is to talk about it with your friends and be supportive to other people.  Additionally, Caroline urges everyone to understand that the things you have accomplished are not just because of luck.

Mimicking the Rabies Virus to Fight Brain Cancer

BMES Board

It seems unlikely that a virus that kills thousands every year would give scientists new insights into effective cancer treatment, but that is exactly what researchers have done with the rabies virus.  Brain tumors are difficult to treat because the blood brain barrier, a membrane that controls what reaches the brain, stops cancer fighting drugs from reaching brain rumors. It is estimated that about 17,000 people die of brain tumors each year.  The rabies virus has the unique ability to pass through the blood brain barrier, giving cancer researchers the opportunity to treat brain cancer by mimicking the rabies virus.

Yu Seok Youn has led a team of researchers at Sungkyunkwan University in Suwon, South Korea in repurposing the rod-like structure that allows the rabies virus to penetrate the brain to fight cancer.  The researchers used rod-shaped, gold nanoparticles that are able to use nerve cell receptors as a method of entering the brain.  These nanoparticles then become concentrated at the brain tumor and are able to absorb heat to kill the cancerous tissue.  Because the nanoparticles are made of gold, they are able to absorb infrared light and radiate enough heat to kill surrounding cells while other brain tissue is spared.  This method of tumor treatment has worked in mice, but has not yet been attempted in humans.  Here is the scientific journal article describing the methods used.

There is some dissension among the scientific community about the true potential of this treatment method.  Some believe that the results of this study are not accurate because rabies usually takes longer to bind than was reported in the study.  Another expert has expressed that it may be possible that the nanoparticles do not all accumulating around the cancer cells, leading to damage of healthy tissue as well as cancerous tissue.  It is apparent that more work must be done to determine the effectiveness of this treatment; however, utilizing the attributes of a deadly virus to fight cancer is an example of an innovative strategy that will push the medical field forward in the future.

Here is an article is Science that provides more information on Youn’s study.

Multiple Oscillators Drive Forward Locomotion in C. elegans

Shelly Teng, Anthony Fouad, & Dr. Christopher Fang-Yen

This summer, I worked in the Fang-Yen lab to study the neural circuit of the microscopic nematode, Caenorhabditis elegans (C. elegans). In particular, our project closely studied how its neural network was able to control behavioral locomotion and movement. Previous studies have shown that locomotion is primarily driven by some combination of spontaneous rhythmic oscillators and the propagation of this signal through the rest of the worm’s body. By using optogenetic techniques, we were able to manipulate various neurons within the worm’s forward locomotion circuit and behaviorally assess how changing a certain neuron had an effect on the worm’s ability to propagate rhythmic movements. Data were analyzed using MATLAB and various worm segmentation software. Results from the study showed that the worm’s forward locomotion circuit is most likely comprised of multiple oscillators that are present through the entire length of the body. These oscillators have the ability to generate spontaneous undulations, and they have some sort of entrainment property that allows them to have specific effects on each other.

In the future, we plan to continue our work in elucidating the functional relation and connectivity of the neural circuit and forward locomotion. Through this project, we hope to better understand the nature of rhythmic locomotion in animals, as it is also relevant to many more complex organisms.

Potential Future Organ Transplants From Human-Animal Chimeras

BMES Board

Lack of available organs for organ transplants leads to the death of thousands every year.  A potential solution has made its way into the spotlight with a paper published in January of 2017: organs from human-animal hybrids.  In this article, Researchers from the Salk Institute detail the insights they gained from their efforts to cross the cells of two different organisms, and allow them to grow into a hybrid animal, otherwise known as a chimera.

The researchers of the Salk Institute created mouse-rat chimeras and human-pig chimeras by injecting the embryo of one organism with stem cells from another organism.  Under the right conditions, embryos were then able to grow into a hybrid organism with the cells of both organisms growing together.  Mice embryos injected with rat stem cells grew into adult chimeras with traits of mice and rats, some even growing gall bladders which have been absent in mice for millions of years.  The human-pig chimera embryos were allowed to develop for three to four weeks before they were taken out of the pigs for analysis.  It was concluded that the human-pig chimeras were developing with about one human cell per every hundred thousand pig cells.

These chimera organs clearly would not be usable in organ transplants due to the high ratio of pig cells; however, the potential for more human hybrid organs exists in the future.  Researchers conducting this study utilized the CRISPR Cas9 system to delete traits from the host embryo that would prevent the injected cells from growing, demonstrating the utility of CRISPR Cas9.  Another insight gained from this study was the delicate developmental timing of injecting stem cells when creating chimeras.  There are complicated moral issues associated with combining human and animal cells into one organism; however, the idea of growing usable human organs for life-saving transplants is exciting.

Here is a National Geographic Article outlining the findings and implications of the study discussed.

A Topic in Bioethics: Bioweapons Event Summary

BMES Board

On Tuesday, 3/24/15, Dr. Matthew Hersch and Dr. Jonathan Moreno led a group of students in a discussion on the ethics of bioweapons. This is an issue that has become increasingly crucial as new technologies are developed, and the accessibility and lethality of bioweapons increases. Dr. Hersch and Dr. Moreno talked about topics that ranged from the various types of bioweapons to the United States’ preparedness for a bioweapons attack against the USA. They also briefly discussed their similarities with chemical and nuclear weapons.

Dr. Matthew Hersch, professor of Engineering Ethics, received his B.S. from MIT in Political Science and his Ph.D. from Penn. A Penn professor since 2009, Hersch has taught 8 courses at Penn, published over 30 conference papers, and won a multitude of prizes. Dr. Hersch is joining the faculty at Harvard University beginning July 2015.

Dr. Jonathan Moreno is a professor of medical ethics and health policy at Penn Medicine. He received his B.A. from Hofstra University, and later his Ph.D. from Washington University. Dr. Moreno has published 21 books and more than 500 papers, book chapters, reviews and op eds. Moreno is an elected member of several national and international bioethics committees. He was also a senior staff member multiple presidential advisory commissions.

Resume Workshop Event Summary

BMES Board

This year, Engineering Week at Penn was held February 23rd-27th. On Monday the 23rd, BMES hosted a resumé/cover letter workshop with guest speaker Rosette Pyne from Career Services. Pyne walked students through the steps to writing a cover letter and building a resume tailored to different applications. She even included memorable anecdotes from past students’ experiences, particularly about proofreading and using one’s own words, to reiterate her points.

For the second half of the event, as they munched on Federal Donuts, attendees broke off into one-on-one resume checks with upperclassmen from BMES and Theta Tau. All in all, Mrs.Pyne’s presentation combined with these resume critique sessions ensured that the event was an informative, yet interactive experience for the mostly freshman and sophomore attendees.

The Degradation and Mechanical Properties of Hydrogels

James Howard, Ryan Wade &  Dr. Jason Burdick

Our first Research Spotlight was written by James Howard, a junior working in Dr. Jason Burdick’s lab.  If you would like to learn more about his work or the other research being conducted by the Burdick lab, feel free to visit their lab website.

The goal of the research was to form a mathematical model that related the strength of hydrogels with a hyaluronic acid (HA) backbone to the enzymatic degradation rate of that hydrogel. Ultimately, this model could be used for future studies that apply to cell culturing, cell delivery, and growth factor delivery.

In degradation analysis, hydrogels were tagged with a fluorescent molecule before cross-linking, and after gelation, these gels were put in varying concentrations of Type II collagenase, which contains matrix metalloproteinases. Every other day, the gels were refreshed with collagenase or buffer, and the supernatant was collected to determine HA release from the network (fluorometric analysis). The results showed that the 4 wt% gels were mechanically stronger than the 2 wt% gels because a larger weight percent corresponds to an increase in cross-linking density, causing the gels to be stronger. The degradable hydrogels completely degraded in response to collagenase because the peptide sequences within the gel are recognized. In contrast, non-degradable gels remained intact in collagenase as the peptide cross-linkers were not recognized by collagenase.

The next step in developing this mathematical model is to measure the Michaelis-Menten degradation parameters of single degradable and non-degradable peptides to incorporate into a statistical model of degradation.

Research Spotlights

BMES Board

This semester, we will be posting Research Spotlights to give BE undergraduates who are working in a research lab the opportunity to share their work with the BE community.  We hope the Spotlights will promote discussions and well as introduce readers to areas of study outside of their own.

If you work in a lab that does biomedical-related research at Penn and would like to write a short summary of the lab’s activities, please email the BMES Board at pennbmes@gmail.com. If you plan to work in a lab over the summer, let us know, and you can submit at article at the beginning of the Fall 2015 semester. Remember to first get permission from your PI!

Plans for Next Semester

BMES Board

We are very excited for the spring semester, as we have a lot in the pipeline which we believe will benefit the BE community.

Our first event of the semester was a talk by Eric Esch, a PhD student in the Huh Lab.  He worked as an engineering consultant for MPR Associates, and spoke to members of the BE Mentoring program about important lessons he learned as an undergrad.  The talk took place on Thursday, 1/22/15 in Raisler Lounge from 12-1pm.

The mentoring program will continue to hold small events to encourage the mentor/mentee relationships that began in the first semester.  We are hoping to hold a spring semester kickoff event in the near future for members to reconnect with each other after the long winter break.

Semester in Review

BMES Board

BMES would like to welcome you back to what is sure to be another fun and fulfilling semester at Penn.

The Fall 2014 semester was a very successful one for us. We won the BMES Outstanding Outreach Award from the national BMES organization for our efforts in spreading awareness about bioengineering to the surrounding community. We also organized a variety of events focused on professional development, community service and academics. One of our biggest events was the BE Alumni Reception. Taking place in the Glandt Forum of the Singh Center for Nanotechnology, undergraduate BE students had the opportunity to speak with alumni about their undergraduate experiences and the careers they are currently pursuing with their BE degrees. Another event was the Healthcare Consulting Panel, hosted in partnership with the M&T Club. The panel consisted of representatives from ZS Associates, PwC, and Simon-Kucher & Partners. It was a great way for students to learn more about healthcare consulting from professionals in the field. In November, we organized a registry drive with Be The Match to allow BE students to join a bone marrow registry and get the opportunity to save the lives of blood cancer patients. We are planning on holding another drive this semester to give even more people the chance to register.