Breaking News
October 19, 2018 - Few Seniors Who Self-Harm Referred for Mental Health Care
October 19, 2018 - Don’t sweat the sweet stuff
October 19, 2018 - URMC researchers discover new approach to deliver therapeutics to the brain
October 19, 2018 - Middlemen suppliers can increase drug prices and hospital bills, say Johns Hopkins researchers
October 19, 2018 - $11 million NIH grant for Clemson University helps launch new center for musculoskeletal research
October 19, 2018 - A new approach identified to control Zika virus, dengue fever
October 19, 2018 - Head Blows Without Concussion May Not Damage Brain, Study Claims
October 19, 2018 - US opioid use not declined, despite focus on abuse and awareness of risk
October 19, 2018 - Next-generation RNA sequencing technology sheds new light on human mitochondrial diseases
October 19, 2018 - UT Southwestern biochemist receives 2019 Breakthrough Prize in Life Sciences for innate immunity discovery
October 19, 2018 - The immune system also plays a key role in day-to-day function of healthy organs
October 19, 2018 - New tool may reveal how the brain structure impacts brain activity, human behavior
October 19, 2018 - Trump Administration announces ‘Winning on Reducing Food Waste’ initiative
October 19, 2018 - For-profit nursing home residents more likely to experience health issues caused by substandard care
October 19, 2018 - Incidence of stroke has risen steadily among marijuana users, show studies
October 19, 2018 - Conceptual framework proposed to examine role of exercise in multiple sclerosis
October 19, 2018 - Near infrared spectroscopy technique for accurate evaluation of chondral injuries
October 19, 2018 - Scientists receive $5.1 million grant to develop stem cell-based therapy for blinding retinal conditions
October 19, 2018 - Shorter physician encounters associated with antibiotic prescribing
October 19, 2018 - In the Spotlight: Enjoying research and exploring opportunities
October 19, 2018 - Physical activity lowers cardiovascular mortality risk in frail older adults
October 19, 2018 - New imaging tool helps visualize how sound-induced vibrations travel through the ear
October 19, 2018 - Key insights into the application, production of bioactive materials
October 19, 2018 - New urea sorbent could speed up the development of wearable artificial kidney
October 19, 2018 - Intensive care patients’ muscles less able to use fats for energy
October 19, 2018 - FDA Advisory Committee Recommends Approval of Dsuvia for the Treatment of Moderate-to-Severe Acute Pain
October 19, 2018 - 48,XXXY syndrome – Genetics Home Reference
October 19, 2018 - Physical exercise improves the elimination of toxic proteins from muscles
October 19, 2018 - How a new system improved wait times for Stanford kidney transplant patients
October 19, 2018 - Nutrition has bigger positive impact on bone mass and strength than exercise
October 19, 2018 - Study finds lack of progress in media representation of nurses over last 20 years
October 19, 2018 - Many people have trouble understanding differences between OCD and OCPD
October 19, 2018 - New family planning app found to be as effective as modern methods
October 19, 2018 - Gastric Banding, Metformin Similar for Improving Glycemia
October 19, 2018 - Physiologist publishes findings on the role of the protein titin in muscle contraction
October 19, 2018 - What digital health companies need to do to succeed
October 19, 2018 - N. Carolina Sees Alarming Spike in Heart Infections Among Opioid Users
October 19, 2018 - Video monitoring of TB therapy works well in urban and rural areas
October 19, 2018 - Determining acid-neutralizing capacity for OTC antacids
October 19, 2018 - Males who spend more time taking care of kids have greater reproductive success
October 18, 2018 - Study to explore bioethics of brain organoids
October 18, 2018 - Environmental conditions may drive development of multiple sclerosis
October 18, 2018 - Genetically modifying zebrafish provides more accurate disease models
October 18, 2018 - Purdue Pharma, Eisai announce positive topline results from Phase 3 study of lemborexant
October 18, 2018 - 5 Strength-Training Mistakes to Avoid
October 18, 2018 - Immune system’s balancing act keeps bowel disease in check
October 18, 2018 - Anti-inflammatory drug effective for treating lymphedema symptoms | News Center
October 18, 2018 - Keeping Your Voice Young
October 18, 2018 - One-time universal screening recommended to tackle increase in hepatitis C
October 18, 2018 - Researchers to develop new stem cell-based strategies for treating vision disorders
October 18, 2018 - Detecting epigenetic signature may help people stay ahead of inflammatory bowel disease
October 18, 2018 - Understanding AFib: Slowing down the dancing heart
October 18, 2018 - Using NMR to Reduce Fraud
October 18, 2018 - New automated model identifies dense breast tissue in mammograms
October 18, 2018 - Mysterious polio-like illness baffles medical experts while frightening parents
October 18, 2018 - Cases of Acute Flaccid Myelitis on the rise across U.S.
October 18, 2018 - Dietary fiber reduces brain inflammation during aging
October 18, 2018 - New tool could help prioritize recovery efforts for the poorest hit by natural disasters
October 18, 2018 - Hundreds of dietary supplements shown to contain unapproved drugs
October 18, 2018 - Active Pharmaceuticals ID’d in >700 Dietary Supplements
October 18, 2018 - Cell death protein also damps inflammation
October 18, 2018 - AI pathology diagnostic tool developed using deep learning technology from Olympus
October 18, 2018 - Health Highlights: Oct. 15, 2018
October 18, 2018 - Largest study of ‘post-treatment controllers’ reveals clues about HIV remission
October 18, 2018 - Bad Blood in Silicon Valley: A conversation with John Carreyrou
October 18, 2018 - ANTRUK’s Annual Lecture sends out message on shortage of funds for antibiotic research
October 18, 2018 - NAM special publication outlines steps to ensure interoperability of health care systems
October 18, 2018 - Novel method uses just a drop of blood to monitor effect of lung cancer therapy
October 18, 2018 - New blood test could spare cancer patients from unnecessary chemotherapy
October 18, 2018 - Training young researchers to work with data volumes arising in the health sector
October 18, 2018 - New Metrohm IC method is reliable and convenient to use for zinc oxide assay
October 18, 2018 - Global AIDS, TB fight needs more money: health fund
October 18, 2018 - Understanding the forces that cause sports concussions
October 18, 2018 - Research points to new target for treating periodontitis
October 18, 2018 - New tool improves assessment of postpartum depression symptoms
October 18, 2018 - From Biopsy to Diagnosis
October 18, 2018 - Sexual harassment and assault linked to worse physical/mental health among midlife women
October 18, 2018 - Stumped by medical school? A Q&A with a learning specialist
October 18, 2018 - Report predicts life expectancy in 2040, Spain comes out on top
October 18, 2018 - Self-lubricating condoms may help raise condom usage
Scientists find fast way to manipulate cell’s cilia

Scientists find fast way to manipulate cell’s cilia

image_pdfDownload PDFimage_print

Scientists at Johns Hopkins Medicine and the National Tsing Hua University in Taiwan say they have found a fast way to manipulate a cell’s cilia, the tiny, fingerlike protrusions that “feel” and sense their microscopic environment. The experiments, performed in mouse cells, may advance scientists’ efforts to not only understand how the nanosized antennae work, but also how to repair them.

A report of their findings appeared online April 30 in Nature Communications.

With few exceptions, most cells in the body have cilia or can grow them. The tiny antenna sense chemicals such as hormones and growth factors, which regulate cell health and growth. Cilia also detect mechanical and physical cues in the body, such as light, gravity, sound and the flow of blood and urine.

When cilia malfunction, a range of human diseases and conditions can occur. For example, problems with cilia in kidney cells can cause polycystic kidney disease, an incurable condition in which fluid-filled cysts interfere with kidney function and which is conventionally treated with dialysis.

Because cilia are so small — 10,000 times smaller than a cell — scientists have long found it challenging to squeeze their tools into such tight spaces to study them.

“When I was a postdoc, a colleague in a neighboring laboratory was studying cilia, and I hoped that by combining his knowledge of the biology of cilia with my expertise in cellular engineering, we could figure out how to manipulate cilia within their tiny spaces,” says Takanari Inoue, Ph.D., professor of cell biology at the Johns Hopkins University School of Medicine and an author of the new report.

After years of work, he says they figured out a way to manipulate a chemical signaling pathway within cilia that controls how molecules are shuttled up and down the length of the tiny structure.

To do it, Inoue and his colleagues in Taiwan used a tool called chemically inducible dimerization, which they say is faster than efforts to manipulate the pathway by rewriting the cilia’s genetic code. The tool, essentially, is a matchmaker — it helps to mesh two specific chemicals together at specific sites within a living cell.

For the new study, Inoue and his colleagues added a protein called FRB to cells from mice grown in the laboratory. The FRB protein is capable of glomming onto a rigid structure within cilia, called a microtubule, which acts as a railway, shuttling proteins up and down the length of cilia.

Then they added a molecule called FKBP to the cells, which is attached to an enzyme that acts as an eraser for a chemical modification in the cilia called glutamylation. The FKBP and enzyme pair floats around the cell until scientists add a chemical called rapamycin, which causes FKBP to get trapped at FRB molecules within the cilia.

Once inside the cilia, the enzyme attached to the FKBP molecule selectively erases the glutamylation modification inside the cilia. It also ignores other signaling pathways.

The scientists call their molecule matchmaking STRIP, for spatiotemporal rewriting intraciliary post-translational modifications.

As a result of rapidly removing glutamylation in cilia, the scientists found that molecules flowed up the cilia, toward the tip, more slowly — about .3 micrometers per second — compared with .4 micrometers per second, using a dead enzyme that doesn’t affect glutamylation.

“We think our technique is faster than existing means of tracking cilia activity and enables scientists to access cilia parts faster and dive into specific chemical modifications for certain amounts of time,” says Inoue.

“Our STRIP system offers a new strategy for precisely controlling microtubule modifications in living cells. With this approach, it becomes possible to understand how microtubules regulate cellular functions and may also serve as a new way to treat human diseases in the future,” says Yu-Chun Lin, Ph.D., an assistant professor at the Institute of Molecular Medicine at the National Tsing Hua University in Taiwan.

Other diseases affected by flawed cilia include a brain disorder called Joubert syndrome, a kidney disorder called nephronophthisis, retinitis pigmentosa and a rare disorder called situs inversus, in which the internal organs of the body are in the reverse location of their normal position.

The scientists also found that microtubules in the mouse cells that are not located inside cilia were not affected when they tinkered with glutamylation.

Inoue and his colleagues also found that the genetic output of a developmental pathway called Hedgehog (which is connected to glutamylation) is decreased in cells treated with STRIP compared with their controls.

Inoue and his colleagues say they now plan to apply STRIP to human cells and look more closely at the molecular process of glutamylation in cilia. They may also use STRIP to control other chemical modifications within cilia.

Source:

https://www.hopkinsmedicine.org/news/media/releases/scientists_develop_method_to_tweak_tiny_antenna_on_cells

Tagged with:

About author

Related Articles