Associate professor AlejandroHeucks biochemistry lab,in collaboration with Worcester-basedMicrobiotix, Inc., has been awarded a two-year, $600,000 NIH Small Business Technology Transfer award to develop a high-throughput screening method to identify inhibitors of a bacterial secretion system that attacks human cells by injecting toxins.Atreatment based on the inhibitorscouldact by a new mechanismtoenhancethe hosts innate immune response to infection, Heucksays.

His co-principal investigator on the project isDonaldMoir,chiefscientificofficer atMicrobiotix,who has many years of experience in anti-infective drug discovery and inhibitors of Type 3-mediatedsecretion.Heuck himself is an expert in Type 3 secretion-mediated translocation, the assembly of thetransloconand its function.

Asheexplains,Bacterial Type 3 secretion systems act like weapons to kill our white blood cells. When our immune system macrophage cells attempt to destroy the intruders, the bacteria use these weapons like syringes to inject toxins to kill the macrophages. Were trying to identify small molecules that block the injection of the bacterial toxins to prevent them from killing macrophages.

The new molecules would be used in combination with antibiotics, he adds.With this method, after the antibiotics wipe out as many of the bacteria as possible, the small molecules would be in place toprotectthebodys ownimmunecells against the injected bacterial toxins. The macrophages would kill the remaining antibiotic-resistant bacteria.

Heuck explains,Sometimes antibiotics dont kill all the bacteria, some of them survive because of resistance. But when we protect the macrophages from the bacterial attack, the immune system can kill the few bacteria that survive the antibiotics.

The researchers plan to first design the new approach to better control thepathogenPseudomonas aeruginosa,which is classified as a serious threat by the Centers for Disease Control. Nearly 30% of pathogens isolated in hospitals are resistant to three classes of antibiotics.

The Heuck labs collaboration withMicrobiotixbegan two years ago afterHeuckand colleagues published a manuscript that triggered thenewidea. The lab won initial support in a translationalmidigrantfrom thecampussInstitute for Life Sciences Models to Medicine (M2M) Center, funds fromthe College of Natural SciencesBridge and Seed Funding program and,more recently, a UMass Faculty Research Grant/Healey Endowment Grant. Theseallowed theresearchersto collect the preliminary data required to move the idea forwardtoward the NIH grant.

Heuck says,Basic researchus alone in the labsometimes leads to an idea that could benefit thepublicbut we dont have the tools or expertise to go to the next step like a company has. I really appreciate that the university has so many mechanisms to help us reach out and make these connections. When university researchers join forces with local small companies, we accelerate the creation of life-saving technologies and stimulate the economic growth of the local industry.

He adds that discovery of a lead inhibitor chemical series will providea compelling basis to obtain additional funding to develop such lead series into a preclinical candidate, and ultimately obtain a novel drug against multi-drug resistantP. aeruginosa.

At a more advanced stage,heplans toseek research partnerships or venture financing to develop the product through clinical proof-of-concept, or Phase 2.Once the clinical proof-of-concept is demonstrated, a corporate partner will be sought for expanded clinical trials and eventual commercialization,Heucksays.

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Heuck's Lab Honored with NIH Small Business Technology Transfer Award - UMass News and Media Relations