How often do you moisturize your skin? Every day? Once a month? Well researchers at Northwestern University in Chicago have given a moisturizer the ability to perform RNA interference and regulate genes.

Topical treatments are common for skin cancers like melanoma, as they can be applied directly to the affected cells. But our skin is very effective at blocking toxins getting into our bodies so the challenge was how to cross that barrier.

Again, enter the realm of nanotechnology, a topic I post about regularly.

This time, the scientists paired gold nanoparticles with small interfering RNA (siRNA) molecules to form a siRNA “sphere.” These miniscule balls were able to penetrate skin cells, and then the specifically-designed siRNA was able to effectively switch off the EGFR gene that codes for the epidermal growth factor receptor protein. EGFR is one of the crucial proteins in pathways to cancer, and can cause cancer cells to go into overdrive and proliferate.

The key factor was the sphere shape, concentrating the nucleic acid in the RNA. Linear nucleic acids can’t get into cells, but spherical ones can.

So what miraculous moisturizer did they use? La Mer? Clinique? Something mixed up in a special laboratory? Nope. They used a cheap, readily available moisturizer.

This type of breakthrough is yet another example of the brilliant strides science can make when one discipline talks to another. In this case, dermatology, cancer and chemistry came together under the remit of the Skin Disease Cancer Research Center at the Feinberg School of Medicine at Northwestern.

I recently blogged about harnessing the power of bioinformatics for cancer research. An interested reader, Linda Zabriske, commented that the blogosphere (and government organizations such as the Bureau of Labor Statistics) has been gradually filling with talk about cancer research and its role in our future. Linda’s tool, the Online Graduate Programs, collates some of these articles and ideas and she’s co-written this month’s post with me, reflecting on Online Graduate Education in Biotechnology.

In past decades, the field of biological science and engineering were considered separate and distinct. Biology dealt with the complexities and wonders of humans, animals and plants, while the engineering (and technology) revolved around mechanics, electronics, and other systems for developing new devices. Recently, however, scientists are creating ways to allow these schools of thought to interact with one another in new and exciting ways through biotechnology.

These breakthroughs have generated a slew of breakthroughs in health, medicine, technology, ecology, computing, telecommunications, the list goes on, with new fields constantly emerging. Case in point: bioinformatics, which was the topic of another DNALC blog post recently. In response, there are several new virtual masters degree programs.

What is Biotechnology?
As part of my role as Evaluation Manager at the DNALC, I’m currently asking biotechnology teachers at community college across America to help me define the term ‘biotechnology.’ (The teachers are participating in an NSF-funded training program, Genomic Approaches to Biosciences). According to the Biotechnology Institute, a nonprofit group that promotes biotechnology education and initiatives, biotechnology is “the use of living organisms by humans.” While most observers associate biotechnology with scientists in white lab coats, its origins stem back to ancient times. Farmers would employ biotechnology techniques to crossbreed plants to withstand adverse weather conditions or to produce more food (see, for example, the chapter on domestication of corn in Weed to Wonder, available as a website, iPad app, or PDF). Livestock owners would selectively breed their animals to provide more meat, carry more weight or run faster in a race.
Importance of Biotechnology
Biotechnology is applying the familiar scientific disciplines of biology and biochemistry, along with the fields of physics, engineering, and computer science, to produce new developments that carry extraordinary potential for the future of mankind. Advances in genetic engineering, nanotechnology, and microbiology have expanded human understanding of some of the most basic and vital processes of life.

Applications of Biotechnology
While many of these research efforts involve medical applications, biotechnology is not limited strictly to prolonging and improving the human body. Agricultural applications, such as genetic engineering of plants and animals (e.g for biofortification), can do the work of several generations of crossbreeding in a much shorter time frame. Other efforts involve the development of biofuels, including biodiesel for use in automobiles, which can reduce the worldwide dependency on fossil fuels and other pollutants.

Careers in Biotechnology
With so many different applications for biotechnology, the opportunities for new careers have been growing at a staggering pace. The DNALC teacher training program mentioned above specifically aims to train graduates for careers in biotechnology, partnering with Bio-Link, the Next Generation National Advanced Technological Education (ATE) Center of Excellence for Biotechnology and Life Sciences. Some students will use their biotechnology degrees in cutting-edge laboratories around the world, while others apply their knowledge as physicians, public health officials, and policy makers. Students also explore the legal, ethical and business applications of biotechnology to understand and resolve the inherent conflicts in
these fields, and become informed citizens.

Degrees in Biotechnology

Two of the top-flight medical schools in the US are endeavoring to give students the online education they need to pursue a career in biotechnology. Harvard University’s Graduate Program in Biotechnology allows students to pursue advanced degrees online. Fields of study include Life Sciences, Management Principles, Bioengineering/Nanotechnology, and Bioinformatics, which is the application of computer technology to solving biotechnology issues. For nearly a century, Johns Hopkins University in Baltimore, Maryland, has been one of the leading medical schools in the country. Today, the school offers students four online degree programs in biotechnology. The programs cover topics ranging from entrepreneurship and federal regulations of the biotechnology industry, to the development of complex computer programs that analyze data from biotechnology experiments.

Just as communications technologies brought in thousands of new jobs in previous decades, biotechnology is revolutionizing the workplace in the 21^st century. As the wave of advancing technology carries this field to new levels, the access to online classes in biotechnology has never been better.

And who knows, maybe one of the new grads may someone harness the power of bioinformatics to find a new treatment for cancer! Watch this space…

Tumor cells are a mosaic of different cell types

For the last decade or so, progressive cancer treatments involved taking samples of tumors, testing the cells to determine the genetic makeup, and then prescribing medicines targeted to specific mutations. There are many benefits to this approach, but it doesn’t always work.

It turns out that tumors aren’t uniform; they are mosaics of cells that can be genetically very different. A recent paper in the New England Journal of Medicine showed that a cell in one area may not be the same as a call in another area (a phenomenon called “intratumor heterogeneity”). So a treatment based on a sample from one area may not work for the whole tumor. Some tumor cells may be resistant to the drug so the cancer persists, or even grows.

In this British pilot study, cells from 9 different locations within a primary kidney tumor, and several metastatic tumors, were analyzed using next generation DNA sequencing. Only 34% of the 118 mutations identified were present in all the samples, and several of the major cancer genes were mutated in different ways in different locations. This turned traditional ideas about cancer cells being “clones” of a single, mutated cell on its head.

Previously, it was thought that a tumor develops when a single cell accumulates sufficient mutations over time that eventually lead to it dividing uncontrollably. Therefore if you could find the original mutation, and target treatment to that, then every cell would react to the treatment. But if the tumor is made up of a mosaic of cells, then they could all react differently to the drug. The researchers then created a phylogenetic “tree,” identifying which cells were more persistent, being in the trunk of the tree. They proposed that if those cells were receptive to a targeted medicine, the treatment might be more effective; if not, less so.

Although this study only involved four patients, the results provide a new way of thinking for researchers and clinicians. If we remove the presumption that all tumor cells are identical, we open the way for more creative thinking about how to tackle the problem.

Recently three high school students took out top honors in science fairs for their projects involving cancer research:

• Angela Zhang from California developed nanotechnology to destroy cancer stem cells and win the 2011 Siemens Competition in Math, Science & Technology;
• Shree Bose from Texas discovered a protein that could help prevent resistance to chemotherapy to take out first prize in the first International Google Science Fair; and
• Michigan native Nithin Tumma won the 2012 Intel Science Talent Search with his investigation of molecular pathways to compare breast cancer treatments.

The budding researchers walked away with a combined $250,000 in prize money for their efforts!

Angela used nanotechnology in a three-pronged approach to eradicating cancer stem cells, similar to my recent post on using DNA nano-robots to deliver cancer drugs to tumor cells. Not only did Angela design a nanoparticle to find the stem cells, and deliver the drug straight to the cells, but she used gold and iron molecules in the nanoparticle to allow non-invasive imaging via MRI and photoacoustic methods. Any one of these discoveries was worthy of an advanced level science fair project, let alone combining all three. As she told ABC News, “I created a nanoparticle that’s kind of like the Swiss Army knife of cancer treatment in that it can detect cancer cells, eradicate the cancer cells and then monitor the treatment response. So the major aim of the project was to personalize cancer medicine.”

Shree investigated how cancer cells become resistant to chemotherapy. Using ovarian cancer cell cultures, she found that the protein adenosine monophosphate-activated protein kinase (AMPK) modulated resistance to the drug cisplatin at different times during treatment. If AMPK was combined with cisplatin early in treatment, it reduced the drug’s effectiveness, but if added later during treatment, it helped maintain effectiveness; in effect, reducing resistance. Shree realized the importance of her work, commenting, “That opens up a lot of new avenues for research.”

Nithin’s project looked at the protein cytokine TGF-A involved in cell signaling, one of the key concepts in the Pathways to Cancer. As I wrote in a past post, we can use the analogy of a car to think about cancer cell growth: tumor cell overgrowth is like pressing down on the accelerator; apoptosis is like applying the brakes. Nithin used computational biology techniques (bioinformatics) to research how to inhibit TGF-A to slow cancer cell growth and decrease malignancy.

Science fairs have been running almost as long as we’ve been teaching science, and giving aspiring scientists an opportunity to shine. Alumni of the Intel competition alone have gone on to win seven Nobel Prizes, two Fields Medals, three National Medals of Science and 11 MacArthur Foundation Fellowships!

So what’s your next science fair project going to be about?

You can find out more about cancer treatments and cell signalling pathways at www.insidecancer.org.

In a brilliant example of multidisciplinary research, Harvard Medical School’s Shawn Douglas, Ido Bachelet, and George Church combined forces to build nanostructures that would mimic the body’s immune system to recognize cancer cells and trick them into self-destructing. Their research is published today in Science but the discovery didn’t just happen overnight. It’s the culmination of several key discoveries going back several years, by researchers around the globe.

In 2006, Paul Rothemund at the California Institute of Technology, discovered  “DNA origami,” where the Watson-Crick base-pairing rules are exploited to create molecules from viral DNA in specific 3-dimensional shapes. The molecules use small, “staple” strands to bind longer strands and hold them in place. In 2009, chemists and nano-technologists at the Danish National Research Foundation’s Center for DNA Nanotechnology then used DNA origami to create a nano-cube that self-assembled, using staple strands to open a lid.

The Harvard group wondered if there was a way to deliver a nano-cube “robot” to cancer cells and kill them. This is where the immunology expertise paid off: antibodies patrol the bloodstream, honing in on specific cells, binding to them, and signalling them to self-destruct. So how can a DNA nano-robot deliver antibodies to the surface of cancer cells? Remember the cube’s lid?

“We could actually make an open-ended container and then all it would need to do is just turn itself inside out,” Douglas said.

A visual rendering of the DNA "nano-robot." Image courtesy of the Wyss Institute.

They created a “nano-clam” with antibodies waiting inside, ready to launch their attack. The nano-clam springs open when one of the staple strands is broken, just like turning a key in a lock.

And the really clever thing? The lock can be designed so that the key is in the shape of certain cancer cells. So when the cube encounters a cancer cell, such as lymphoma or leukemia cells, it springs open, exposing antibody fragments to the surface of the cell in a “surgical strike.” Unlike chemotherapy, which doesn’t discriminate between cell types, these DNA nano-robots only strike down cancer cells, leaving good cells alone.

The beauty of this discovery is that the underlying mechanism can be adapted for different diseases, by using different combinations of locks and antibodies. As the Danish chemist Kurt Gothelf commented, “People have been talking a lot about robots that enter your body, and go to a place where something is wrong and fix it. This is the first example that this might come true one day.”

The next step is to work out scalability. The current research was in Petri dishes in the lab, with 100 billion copies of the robot, but trillions are required for animals and humans. And the robot needs to become more robust to travel through the bloodstream, rather than through a pipette. Our body is very adept at getting rid of foreign bodies so they have to figure out a way for the nano-clams to swim “under the radar.”

Watch this space…

Researchers have known for a while that not only are glioblastoma multiforme cells highly resistant to chemotherapy, but they can also deftly migrate away from sites of radiation or surgery, setting up camp and regrowing in other parts of the brain. This means that brain cancer is notoriously difficult to treat and the prognosis is almost always grim.

Last year the New York Times described Hanahan and Weinberg’s Hallmarks of Cancer as follows:

“Through a series of random mutations, genes that encourage cellular division are pushed into overdrive, while genes that normally send growth-restraining signals are taken offline. With the accelerator floored and the brake lines cut, the cell and its progeny are free to rapidly multiply. More mutations accumulate, allowing the cancer cells to elude other safeguards and to invade neighboring tissue and metastasize.”

This is a nice analogy, relating overgrowth of cells paired with lack of cell death (apoptosis) as the accelerator and brakes of a car.

However Amy Keating and colleagues at the University of Colorado Cancer Center focused on the car’s GPS system. They published data in Nature: Oncogene showing that when a receptor tyrosine kinase involved in cancer cell growth, Mer, is switched off, significantly less cancer cells migrate to neighboring tissue in cultured laboratory cells. Keating found that not only does Mer interfere with the molecular signaling pathway, but also the cytoskeletal organization (the structure of the cell).

In other words, the Mer switch interferes with the electrics of the GPS system as well as the steering wheel of the car.

This added to their previous finding that Mer could increase some brain cancer cells’ sensitivity to chemotherapy.

So Mer inhibition could be a “double whammy” approach to treating brain cancer: kill as many cancer cells as possible and stop those remaining from migrating.

This year, we found the answer.

As part of my job as a producer at the DNA Learning Center, I evaluate our suite of resources, including websites, teacher training workshops and apps. We recently completed the evaluation of our cancer biology website, Inside Cancer, which included conducting experiments in 2010–11 to see if the site improves student learning in genetics and cancer biology.

There is increasing pressure on us to go beyond anecdotal reports of teacher satisfaction with new resources – to sophisticated studies of how those resources impact students in the classroom. This is a big task, considering that website developers seldom have direct access to students to assess program impact or effectiveness. Evaluation studies require much effort devoted to recruiting teachers and insuring that they generate matched sets of comparable student data. Learning takes place in complex environments with many interacting institutional and personal variables, and controlling for these is daunting.¹

In our study, five high school and college teachers from five states were selected from Inside Cancer teacher trainer workshop attendees. These teachers used Inside Cancer to teach 297 students in 13 classes at three high schools (two public and one Catholic girls-only school), a 2-year college, and a 4-year college. The institutions were in city, suburban, and urban locations and ranged from 250 to 10,000 students, with an average class size of 24 students. High school classes involved in the study were biology (n=94), health (n=37), and biotechnology (n=60). College classes were environmental science, nutrition, life science (n=57) and online biology (n=49). Topics taught included hallmarks of cancer, effects of smoking, cell signaling, mutations, and oncogenesis. Teachers used Inside Cancer in class, or as a resource to complete an assignment and quiz. The median age of student participants was 18.4 years and 71.0% were girls.

To control for differences between teachers and students we used a crossover repeated‐measures design, in which each student participated as both an experimental and control subject.² For the first topic, class A used a DNALC Web site for classwork, and class B used lectures, textbooks, or other Web sites (Figure 1). The classes then switched conditions for the second topic, so that each student learned one topic using a DNALC Web site and one topic using another resource. Students completed a quiz after each topic, which allowed comparison of how well each student learned with and without the use of a DNALC Web site. This study design allowed us to examine how Inside Cancer was used in different cohorts of students in different settings.³

Figure 1. Crossed, repeated-measures study design for evaluation of InsideCancer.org.

* Included PowerPoint lectures and other websites, such as NIH.

Strikingly, students’ quiz scores were significantly higher when using Inside Cancer: 85.0% ± 20.8 versus 73.8% ± 21.3, t₂₉₆=7.361, P < 0.001 (Figure 2).

Thus, we now have a practical and supportable answer to that difficult question: an engaging website can potentially increase student learning by about one letter grade.

So go check out Inside Cancer – it may well help you increase your grades!

This blog post is based on an excerpt from a paper that appears in the December 23 issue of the journal, Science .

1) L. Cohen, L. Manion, K. Morrison, Research Methods in Education (Routledge, Oxford, ed. 6, 2007).

2) B. Jones, M. Kenward, Design and Analysis of Cross‐Over Trials (Chapman and Hall, London, 2003).

3) Papay, J. Different tests, different answers: The stability of teacher value-added estimates across outcome measures. American Educational Research Journal 2011;48(1):163-93.

So researchers in the UK brought in the big guns – bioinformatics.

Cancer Research UK has set up seven British centers to start collecting 9,000 tumor samples from a wide range of cancer patients to create a DNA database. Researchers will extract DNA from these tumors and scan them for a series of key genes involved in tumor development. The results will then be cross-checked against a range of cancer treatments, to create a map of which treatments work best for cancers associated with which particular genes.

This is based on the concept of pharmacogenomics: certain genes predispose people to respond to certain drugs in certain ways. We can already test a cancer patient for a single gene, knowing how tumors with that gene respond to a particular drug. However currently we don’t have a way of testing a broad panel of genes. And to compound the problem, we don’t have a way of quickly and accurately sharing information between labs in the same city, across the country or internationally.

Again, enter the power of bioinformatics.

With the proposed cancer DNA database, a doctor might analyze a patient’s tumor sample and prescribe a tailored treatment plan within a very short period of time, perhaps as little as two weeks.

As Professor Matthew Seymour, director of the National Cancer Research Network (NCRN) in the UK, recently stated, “We have to get clever about how to target drugs. Medications for cancer have to be personalized because no two cancers are identical.”

Bioinformatics research is increasing at an exponential rate. DNA sequences are available to anyone with an Internet connection – along with free bioinformatics tools to explore sequence data, predict the presence of genes, and compare features shared between organisms.

The DNALC has been working in DNA sequencing and bioinformatics for over a decade, developing intuitive, visually appealing computer tools for teachers and students to quickly learn the rudiments of gene analysis and integrate bioinformatics with biochemistry labs.

If you want to find out more, check out:

• G2C Online Bioinformatics section
• DNAi: Applications > Genes and medicine > Genetic profiling
• Gene Boy, a fun, intuitive Flash interface to analyze DNA sequences.
• Sequence Server, a database and personal workspace for students to conduct phylogenetic analyses using their own DNA sequences.
• DNA Subway, a platform that uses the metaphor of a subway network to provide students access to various bioinformatics workflows.

Well you may actually be one of the lucky ones! Your immune system’s sensitivity may be protecting you from contracting brain cancer.

Researchers at the University of Illinois at Chicago asked over 1,000 hospital patients about their allergy histories. Astonishingly, patients who had high-grade glioma, a form of brain cancer, reported significantly less allergies than those without the cancer. This double negative is a bit tricky to interpret, so flipping this statistic on its head: having allergies reduced the likelihood of having brain cancer!

And it doesn’t stop there. The researchers also found that having more than one allergy provides even more protection. As the team leader, oncologist Bridget McCarthy, stated: “The more allergies you have, the more protected you were.”

But don’t be alarmed if you don’t have allergies; brain tumors are still very rare and this is just a preliminary finding from a small study sample.

The intriguing question now becomes, “Why?” How does an overactive immune system protect against cancer? We know that our body’s immune system launches attacks on foreign cells, such as tumor cells, so maybe this is where the answer lies.

Read the paper here.

Read more about our body’s immune response to cancer in the “Avoiding Detection” section of Inside Cancer here.

Researchers at the University of California Los Angeles and Ohio State University Comprehensive Cancer Center are investigating a new treatment for glioblastoma, the deadliest form of brain cancer. Their paper, out this week in Cancer Discovery, shows how blocking a mechanism involved in cell metabolism and triggered by a cancer gene can reduce brain tumors.

Glioblastoma affects about 18,500 Americans each year, with less than a third surviving. The brain tumors are very difficult to remove as the cancer cells invade surrounding brain tissue. To make matters worse, some people are genetically predisposed to resisting chemotherapy or radiotherapy.

The researchers looked at the cellular mechanism that involves an over-active PI3K signaling pathway. This pathway is stimulated by a gene variant called EGFRvIII, which is present in nearly half of all glioblastomas. The gene variant also switches on a transcription regulator, increasing the activity of the low-density lipoprotein (LDL) receptor. This increases the uptake of LDL, providing more cholesterol for the brain tumor cells to feed on, grow and survive.

The number of LDL receptors was reduced in these experiments by activating an alternative receptor, the nuclear Liver X Receptor. This then caused the cholesterol to be transported back out of the tumor cells using an ABCA1 protein pump. Without the extra cholesterol, the greedy brain tumor cells eventually starve and die.

The good news is that this signaling pathway is not just confined to glioblastomas so this therapy may eventually be used to treat other forms of cancer.

So it’s yet another reason to cut out the eggs, cream and butter and have oatmeal for breakfast!

Guo D, Reinitz F, Youssef M, et al. An LXR agonist promotes glioblastoma cell death through inhibition of an EGFR/AKT/SREBP-1/LDLR-dependent pathway. Cancer Discovery 2011; early online.

(For more on signaling pathways in cancer cells, check out “Pathways to Cancer” @ the Inside Cancer website.)