Joel Kralj

Interview With a Scientist: Joel Kralj, Electromicist

Anonymous — Mon, 19 Feb 2018 14:54:55 +0000

Interview With a Scientist: Joel Kralj, Electromicist Anonymous (not verified) Mon, 02/19/2018 - 07:54

BioFrontiers

[video:https://www.youtube.com/watch?time_continue=7&v=TnY652YC2Pc]

Every one of our thoughts, emotions, sensations, and movements arise from changes in the flow of electricity in the brain. Disruptions to the normal flow of electricity within and between cells is a hallmark of many diseases, especially neurological and cardiac diseases.

The source of electricity within nerve cells (i.e., neurons) is the separation of charge, referred to as voltage, across neuronal membranes. In the past, scientists weren’t able to identify all the molecules that control neuronal voltage. They simply lacked the tools. Now, University of Colorado biologist Joel Kralj has developed a way to overcome this hurdle. His new technique—combining automated imaging tools and genetic manipulation of cells—is designed to measure the electrical contribution of every protein coded by every gene in the human genome. Kralj believes this technology will usher in a new field of “electromics” that will be of enormous benefit to both scientists studying biological processes and clinicians attempting to treat disease.

In 2017, Kralj won a New Innovator Award from the National Institutes of Health for his work on studying voltage in neurons. He is using the grant money to develop a new type of microscope that will be capable of measuring neuronal voltage from hundreds of cells simultaneously. He and his research team will then attempt to identify the genes that encode any of the 20,000 proteins in the human body that are involved in electrical signaling. This laborious process will involve collecting hundreds of nerve cells, genetically removing a single protein from each cell, and using the new microscope to see what happens. If the voltage within a cell is changed in any way when a specific protein is removed, the researchers can conclude that the protein is essential to electrical signaling.

In this video, Kralj discusses how he plans to use his electromics platform to study electricity-generating cells throughout the body, as well as in bacterial cells (see our companion blog post “Feeling Out Bacteria’s Sense of Touch” featuring Kralj’s research for more details).

Dr. Kralj’s work is funded in part by the NIH under grant 1DP2GM123458-01.

Find this story on Biomedical Beat

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Colorado Public Radio features Joel Kralj

Anonymous — Fri, 01 Sep 2017 15:23:12 +0000

Colorado Public Radio features Joel Kralj Anonymous (not verified) Fri, 09/01/2017 - 09:23

Here's A 'Touching' Discovery About Bacteria

If University of Colorado scientists are right, bacteria have a sense of touch. Meaning, the little critters can detect the cells they need to glom onto to cause an infection.

University biologist Joel Kralj says his lab showed bacteria have electrical activity going on inside them. If scientists can find a way to block that activity, they may be able to develop drugs for infectious diseases. The study, recently published in the Proceedings of the National Academy of Sciences, is the latest focus of our series, Beta Test, exploring scientific and technological breakthroughs in the state.

Visit CPR to hear Joel's interview.

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Bacteria have feelings, too

Anonymous — Tue, 15 Aug 2017 21:31:19 +0000

Bacteria have feelings, too Anonymous (not verified) Tue, 08/15/2017 - 15:31

Ula Chrobak

For humans, our sense of touch is relayed to the brain via small electrical pulses. Now, CU Boulder scientists have found that individual bacteria, too, can feel their external environment in a similar way.

In a new study, CU Boulder researchers have demonstrated that E. coli bacteria cells get excited when poked, sending out voltage induced calcium ion signals—the same way a vertebrate’s sensory nervous system works. The results are believed to be the first documented observation of electrical excitability in individual bacteria cells.

The findings, which could advance fundamental bacteria research and may eventually aid drug development for infectious diseases, were published today in the journal Proceedings of the National Academy of Sciences.

“People typically think that [bacteria] are these little things, that all they are doing is trying to divide and create more energy,” said Giancarlo Bruni, a doctoral candidate in CU Boulder’s Department of Molecular, Cellular, and Developmental Biology and the lead author of the new research. “[But] we’re not all that different.”

Scientists have long known that bacteria respond to certain chemical cues. Feed them sugar, and their populations explode. Douse them in antibiotics and their cell walls rip apart. More recently, though, scientists have noticed that physical signals, too, seem to activate these microbes. For example, Salmonella become more efficient at infecting human cells when placed on a stiff surface as opposed to a soft one.

“What we think could be happening is that they’re using these electrical signals to modify their lifestyle,” said Joel Kralj, the senior author of the study and an assistant professor in MCDB and the BioFrontiers Institute.

To study how bacteria feel their surroundings, the team inserted special genes into E. coli bacteria that glow when calcium ions or electricity pulse through them. The cells were placed in a sticky substrate under a microscope. Left alone, the cells remained dim. But when the scientists pushed a pad against them, the bacteria lit up. The sparks of light indicated that proteins, ions and electricity were moving around in the bacteria.

The results indicate that bacteria and other creatures share a common tool for sensing their environment—an electrical pathway with the same functionality as human sensory neurons. From an evolutionary perspective, this signaling trait could be billions of years old and used by some of the oldest organisms on Earth.

The study also sheds new light on bacterial activity with regard to infection. For example, when exposed to antibiotics, a few bacteria cells with unique electric signals usually survive. These survivors then go on to reproduce and share their drug-resistant capabilities with other bacteria, eventually rendering the antibiotic useless.

The CU Boulder researchers now plan to study how bacteria’s electric pulses are used to sense when to infect human cells. In the future, they hope to test for small, masking molecules that can dull these signals when introduced. Such molecules could eventually translate into drugs that help treat bacterial infections and overcome antibiotic resistance.

“If we can block bacterial electrical activity, they may be less likely to infect, because now they don't know that they have landed on your soft delicious gut cell,” said Kralj. “We could cut their hands off so they can no longer feel.”

Additional co-authors of the new study include Andrew Weekley and Benjamin Dodd of MCDB and BioFrontiers. The National Institutes of Health and the Searle Scholars Program provided funding for the research.

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Giancarlo Bruni named Gilliam fellow for minority mentorship

Anonymous — Mon, 14 Aug 2017 14:00:00 +0000

Giancarlo Bruni named Gilliam fellow for minority mentorship Anonymous (not verified) Mon, 08/14/2017 - 08:00

The Howard Hughes Medical Institute (HHMI) has announced today the 2017 Gilliam Fellowship awardees—exceptional doctoral students who have the potential to be leaders in their fields as well as the desire to advance diversity and inclusion in the sciences. CU Boulder Graduate Research Assistant Giancarlo Bruni is one of 39 recipients.

Bruni is currently pursuing a PhD in molecular, cellular, and developmental biology on the topic of bacterial electrophysiology. Prior to starting his graduate work at CU Boulder, he held research positions at Teleos Therapeutics and Massachusetts General Hospital.

Bruni also serves as a mentor to underrepresented groups through CU Boulder's SMART program, a 10-week summer session that helps level the playing field for underserved students who have not had the opportunity to participate in authentic research. He also worked with undergraduate students through the Colorado Advantage Program, encouraging them to pursue a graduate education by discussing his own experiences as a CU Boulder graduate student.

Read the HHMI news release published today.

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Kralj NIH Innovation Award

Anonymous — Tue, 04 Oct 2016 06:00:00 +0000

Kralj NIH Innovation Award Anonymous (not verified) Tue, 10/04/2016 - 00:00

BioFrontiers

Innovator Award winner brings to light the electrical changes in cells

Electric voltage powers life: Our brains use electrical transients to process every thought and every heartbeat arises from voltage changes in heart cells. Traditional measurements of voltage inside cells involve scientists making tiny wires and impaling cells, exactly the same way you could measure voltage flowing through a copper wire. However, due to the small size and fragile nature of cells, it has been technically impossible to measure voltage in neurons in a high throughput manner.

Assistant Professor in Molecular, Cellular and Developmental Biology, Joel Kralj, a BioFrontiers Institute faculty member, became interested in measuring cellular voltage as a postdoctoral researcher and developed a protein based sensor that converts changes in voltage to changes in fluorescence, finally bringing to light the electrical changes in cells.

“The fact that we can convert changes in voltage to something visible allows us to make movies showing these biological processes,” says Kralj, “And because it’s really easy to take a movie, we now have a way of collecting vast amounts of voltage data without a physical connection to the cell, which is faster and easier.”

Kralj recently won a New Innovator Award from the National Institutes of Health for his work on voltage in neurons. According to the NIH, the New Innovator Award supports “unusually innovative research” from young investigators like Kralj. The NIH does not award these grants easily, giving out only about 50 per year. The program is meant to support creative researchers doing high risk, high-impact science—a description that Kralj easily matches

As part of this award, Kralj will receive $1.5 million to support his research, and the Innovator Awards allow more flexibility in spending than most grants. He plans to spend the grant money to develop automated microscopy hardware that will be capable of measuring neuronal voltage from hundreds to thousands of conditions. Kralj is joining Andrew Goodwin, assistant professor of Chemical and Biological Engineering, as CU Boulder’s only Innovator awardees.

In order to study neurons Kralj plans to focus on the approximately 20 thousand proteins that transmit genetic information to find out how each protein affects voltage in neurons. This intensive process will involve removing a single protein in each measurement to see how its removal impacts the cell. Kralj will then create a database that includes the effects each of the 20 thousand proteins on the electrical changes in neurons—changes that lead to neurological diseases like epilepsy and Amyotrophic Lateral Sclerosis, or ALS.

“I am hoping that our sensors, and the database we’re creating, will help us identify the full complement of proteins essential for normal function, and also how their absence might give rise to disease. The New Innovator Award is going to give me the flexibility to follow a lead in this research,” says Kralj.

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Cracking the code on bacterial voltage

Anonymous — Mon, 13 Apr 2015 06:00:00 +0000

Cracking the code on bacterial voltage Anonymous (not verified) Mon, 04/13/2015 - 00:00

BioFrontiers

Searle Scholars Award winner is cracking the code on bacterial voltage

Electric voltage powers life – Our brains use electrical transients to process every thought; every heartbeat arises from voltage changes in heart cells. Despite its importance, voltage changes in bacteria were never really studied because the cells were just too small to measure. In fact, biologists historically assumed that these voltage changes were only present in plants and animals. BioFrontiers Institute faculty member, Joel Kralj, an Assistant Professor in Molecular, Cellular and Developmental Biology, developed a method to encode a fluorescent protein into bacterial cells that allow it to become visible, revealing how bacteria use electricity to stay alive.

“Voltage really is everywhere, and life has harnessed it for billions of years in order to evolve. That’s what is amazing,” says Kralj. “Finding these electrical transients in bacteria gives us an entirely new perspective on their evolution.”

Kralj recently became a Searle Scholar for his work on voltage in bacteria. The Searle Scholars Program supports the research of scientists who recently started their appointments at the assistant professor level, and who are in their first tenure-track position at one of 153 participating academic or research institutions. Kralj was one of 15 researchers who were named Searle Scholars this year. As part of this award, he will receive $100,000 per year for three years to support his research.

The evolutionary story of bacteria is interesting enough but Kralj is looking at how bacteria use voltage changes to access hosts or signal other bacteria to colonize a host. The equipment he uses is highly specialized with fluorescent monitors developed specifically for use in bacteria, and a laser microscope to measure the tiny changes in voltage. Kralj’s lab is relatively new. He joined BioFrontiers last year and is in the process of staffing for his research. He is looking forward to using the funds from the Searle Scholars program to build more equipment to do bacterial research, including automatic scanning microscopes.

Although his research subjects are small, Kralj’s research has the potential to make a big impact. He is unlocking the secrets around how bacteria are using voltage to survive antibiotic exposure. He’s hoping to discover whether many of the antibiotic resistant “superbugs” are staying alive because they are modulating their voltage to attack hosts, colonize and evade the drugs developed to kill them. If Kralj finds this to be the case, he hopes to understand how voltage could be inhibited in bacterial cells so that antibiotic drugs could be more effective.

“The Searle Scholar grants are going to give me the flexibility to follow a lead in this research,” says Kralj. “Researchers looked for twenty years to find a way to measure this voltage, and now that we can measure it, there is so much to study.”

The University of Colorado in Boulder currently has six other Searle Scholars, including Natalie Ahn, Min Han, Arthur Pardi, Roy Parker, Gia Voeltz and Ding Xue.

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