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Toxin From Coral-reef Bacteria Could Become Next-generation Cancer Drug

University of Michigan (U-M) and Scripps Institution of Oceanography at UC San Diego researchers have acquired a new molecular tool that could help them transform a toxin from coral-reef bacteria into a next-generation cancer drug.

U-M Life Sciences Institute researchers David Sherman and Janet Smith led a cross-disciplinary team that uncovered new functions for an ancient, well-known family of proteins found in many organisms, from microbes to humans.

The Sherman team, along with William Gerwick of Scripps' Center for Marine Biotechnology and Biomedicine and the Skaggs School of Pharmacy and Pharmaceutical Sciences at UC San Diego, analyze chemical compounds pulled from marine organisms living in coral reef sediments, blue-green algae, sponges and soft corals. They look for substances, such as bacterial toxins, that can kill or disable cancer cells in the laboratory. Currently, more than a dozen such compounds from marine sources are in pre-clinical or clinical trials as cancer therapeutics.

One such substance is curacin A, a leading anti-cancer drug candidate first derived from a Caribbean coral reef cyanobacterium, L. majuscula, in 1994 by Gerwick's group. In the lab, curacin A is effective against colon, kidney and breast cancer cell lines.

Sherman and his colleagues have been trying to understand how the biochemical machines inside L. majuscula assemble the curacin A molecule. In 2004, the group published a blueprint showing all the proteins that are responsible for making the curacin A molecular chain.

Since then, they've focused on determining the functions of the roughly 60 biological catalysts used in the assembly line-like curacin A synthesis process. The team's latest finding is that the first links in the curacin-A chain include a member of the GNAT family of proteins, a group of enzymes that has long been known to play roles in gene regulation, hormone synthesis and antibiotic resistance.

While Sherman's group carried out the enzymology for the study, Smith's team captured X-ray crystallography images of the GNAT enzyme's structure. Smith is director of LSI's Center for Structural Biology. Gerwick's team made the original discovery of curacin A and provided the cyanobacterial DNA for this study.

L. majuscula is a cyanobacterium, which are among the oldest organisms on Earth. Roughly 3 billion years ago, cyanobacteria began producing atmospheric oxygen that, much later, allowed more complex life forms to emerge. In the L. majuscula bacterium, the curacin A toxin likely performs a defense function, possibly protecting the microbe from predators.

This research is detailed in the November 9 issue of the journal Science.

Adapted from materials provided by Scripps Institute Of Oceanography.

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Dive The Best Wrecks of The World

RMS Titanic Dive Expedition

  One-sixth of a mile long the opulent RMS Titanic took the hearts of the world when she sank 12460 feet (3,750 metres) to the bottom of the Atlantic in 1912 taking hundreds of lives with her; now over 90 years later her mystique and grandeur still captivates people around the world. Pay your respects to the wreck as you glide over her decks, now encrusted in magnificent soft corals and anemones. There is no more famous shipwreck in the world and you are now offered the chance to witness and pay respect to this monument. Expedition to ‘inner space’ You will journey to the Titanic aboard the MIR I and II submersibles, deep-dive vessels capable of reaching ocean depths of 20,000 feet. Housed aboard the mother ship Akademik Keldysh, the two MIR submersibles are part of a group of only four deep-diving vessels available to the world's scientific community. Constructed of special nickel steel, they are specifically designed to withstand the enormous pressures that exist in the depths of the oceans. Each MIR's habitat compartment is 7' (2.1m) diameter, accommodating three persons. There are no traditional bathroom facilities on board. Air pressure inside the habitat remains at a constant one atmosphere; the air is recycled in a manner similar to that used onboard spacecraft. During the dive, there will be a drop in temperature (to approx 54F or 12C) and some slight internal condensation.

Down into the Deep :

Following a final briefing, you'll enter the submersible, then the Keldysh's on-board crane will lift you and the MIRs into the Atlantic's chilly waters. After pre-dive testing, ballast water will be pumped into the tanks and your adventure into the deep will begin. Three Plexiglas portholes, each 7 inches thick, will be your windows to this undersea world. By 1,000 feet, all traces of sunlight will be gone and you will be immersed in total darkness. To conserve power, the MIR submersibles run without external lights, however, the pilot will occasionally switch on the lights to observe passing marine life. Some marine life require no viewing lights; be sure to look for these tiny bioluminescent creatures as you descend. By 4,000 feet, the interior of the MIR starts to cool and your extra clothing comes in handy. Topside, the Keldysh (never out of voice contact) will help navigate the MIR to the wreck site.

Observing Titanic :

As you reach your destination you are at 12.500ft below the surface. The MIR's large halogen-mercury-iodine lights will unveil to you the remains of the R.M.S. Titanic. The ship is in two distinct sections: the demolished stern and the bow, separated by nearly 2,000 feet. The MIRs will spend 2-3 hours exploring the wreckage as well as the surrounding debris field. An outside still and video camera will record your experience; an 8mm video inside the MIR will chronicle the expedition's operations as well as your reactions. Upon completion of the mission, ballast water will be pumped out and the MIR will begin its ascent. Once you return to the surface, the MIR will be lifted back on board the Keldysh and you will be treated to a hot Russian sauna followed by a debriefing.

The Akademik Keldysh is the best deep-diving support vessel in the world. Owned and operated by the Moscow-based P.P. Shirshov Institute of Oceanology, its crew of scientists and technicians has worked together for 15 years, participating in deep-dive expeditions all over the world. In addition to its 17 laboratories, the Keldysh features a specialized library covering underwater archaeology, oceanography, and deep-sea exploration. Your quarters aboard the Keldysh, while not lavish, will be comfortable and spacious. Meals will be first-class, prepared by a European chef and highlighted by the occasional Russian specialty. Satellite communications equipment will be available for contact with those at home.

Fitness and experience requirements :

Anyone with a sense of adventure can dive on a deep submersible dive. Submersibles are all operated at one atmosphere – diving is akin to driving your car. However dives are approximately 10-12 hours in duration, the submersibles are small and the following medical conditions may prevent you from participating in diving.

• History of myocardial infarction(s), cerebrovascular accidents (e.g. stroke, brain haemorrhage, etc.), coronary artery disease and angina pectoris, cardiovascular disease with shortness of breath or pulmonary disease with shortness of breath
• Diabetes mellitus, poorly controlled or insulin dependent
• Severe to moderately severe asthma
• Conditions associated with urinary or bowel incontinence or leakage and flatulence
• Conditions such as marked obesity and back or joint disabilities which preclude entering, exiting and spending hours in close, cramped and perhaps uncomfortable positions
• Anxiety, emotional depression and/or various psychiatric disorders
• History of seizure disorders, severe or disabling surgical procedures
• Each proposed participant (passenger) must provide a list of his/her current medication, prescription and non-prescription and should have adequate amounts of medications with him/her to last the duration of the trip.

What to bring and/or wear :

• The following contains helpful information for you to prepare for your Operation Titanic Voyage. Please keep in mind that weather in the North Atlantic is quite unpredictable, and it’s best to be prepared for possible cold, wet days. It is essential to maximize the versatility of your travel wardrobe by packing clothing that can be layered. Wash and wear, lightweight natural fabrics are recommended. As you pack, consider your own internal thermostat and personal tastes, and adjust accordingly.

• Shipboard Clothing
This is a working research vessel (not a cruise ship), so please pack accordingly. Casual clothes such as jeans, sweatshirts and T-shirts are acceptable. Informal clothes for the occasional party are also recommended. For footwear, water-resistant, rubber-soled shoes, deck shoes, sneakers, or tennis shoes with good traction are suitable. A swimsuit for the sauna is recommended. Workout clothes for the gym and volleyball court are also a suggestion.

• Expedition Clothing
As it may become chilly in the submersible, warm clothing that can be layered is recommended. A waterproof jacket is good to have on deck. Following are suggested items for your dive and time spent on the deck: Fleece jacket and pants: Ideal for the submersible Long underwear: Silk and polypropylene are highly recommended for extra warmth. The trim fit adds warmth and comfort without adding bulk. Sweaters: Bring 1-2 sweaters. We also recommend a turtleneck (preferably polypropylene or silk). Hat/Light Gloves/Scarves: It might get chilly on deck and in the submersible. Warm Socks: Make sure you have an ample supply of warm socks. Again, silk or polypropylene can be worn as liners and wool for the heavier outer layer. Waterproof Warm Booties: These are worn while in the submersible.

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For more information on this "Once in a Lifetime" Experience Please contact us

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