Michael Klemba - Finland

What I Did

On March 15-16, 2019, I visited Dr. Tapio Nevalainen, an experienced medicinal chemist in the School of Pharmacy at the University of Eastern Finland in Kuopio, Finland. Two years ago, Dr. Nevalainen generously provided us with some novel small-molecule inhibitors of a class of enzymes termed “serine hydrolases”. We have discovered that some of these compounds are able to block lipid metabolism in the human malaria parasite Plasmodium falciparum and we are very interested in further developing these molecules as chemical probes and drug leads. This work has led to the submission of an NIH R21 proposal with Dr. Nevalainen as a collaborator. The purpose of the visit was solidify the nascent collaborative relationship and to explore additional opportunities for research funding. 

To kick things off, I gave a presentation on my group’s studies on fatty acid and lipid metabolism in the malaria parasite, titled “Interrogating fatty acid and lipid metabolism in the human malaria parasite Plasmodium falciparum”. Ten research scientists from the School of Pharmacy were in attendance. The goals of the presentation were: to i) introduce the biological system (i.e., the malaria parasite residing within human erythrocytes); ii) define our research questions pertaining to parasite fatty acid and lipid metabolism; iii) report our results to date with Dr. Nevalainen’s compounds; and iv) articulate a vision for future collaborative efforts to build on our promising findings.  

Other activities included: discussions with Dr. Nevalainen (summarized in “Short-term Outcomes), a tour of the School of Pharmacy, and several “relationship-building” activities with Dr. Nevalainen (visit to Puijo Tower; participation in a game of floorball, an indoor hockey sport; and ice skating). 

Short-term accomplishments and long-term goals

1) Appreciation of the research interests and capabilities of both sides of the collaboration. I was able to convey to Dr. Nevalainen, with a depth that is not possible through telephone or skype conversations, the ways in which his expertise and efforts will contribute to the generation of new knowledge regarding critical metabolic pathways in an important human pathogen. Conversely, I gained an appreciation of Dr. Nevalainen’s current interests. This mutual understanding of research objectives and skill sets establishes a solid foundation for our collaboration.

2) Plans for a joint publication.  Dr. Nevalainen and I developed plans to prepare a co-authored manuscript describing our results to date. I anticipate submission of this manuscript to a peer-reviewed journal within the next 6 months.

3) Plans to progress with proposed collaborative studies. We strategized on ways to initiate collaborative studies prior to review of my R21 proposal, which would fund Dr.Nevalainen’s efforts. Dr. Nevalainen currently has limited funds but expressed a willingness to begin purchasing reagents for the syntheses outlined in the R21 proposal, with the goal to quickly begin work upon obtaining project funding. I explained how the NIH grant proposal submission process works. 

4) Plans to take the collaboration in a new direction. In my presentation, I described our recent discovery that one of Dr. Nevalainen’s compounds blocks the malaria parasite’s ability to scavenge fatty acids from a class of lipids termed lysophospholipids. One of my goals for this visit was to assess Dr. Nevalainen’s interest level for extending our collaboration, which would involve the synthesis of a set of compounds distinct from those described in the R21 proposal. He was enthusiastic about extending our collaboration in this direction.

The long-term goal of the collaboration is to develop novel chemical tools with which to discover critical metabolic processes in the human malaria parasite. This will require a stream of funding to support both Dr. Nevalainen’s medicinal chemistry efforts as well as my group’s characterization of his compounds. A collaborative R21 proposal including Dr. Nevalainen as a collaborator is under review at NIH. In addition, I anticipate the preparation of an NIH R01 proposal in the near future that will include the research direction described in item #4 above. Once research efforts get underway, I expect that co-authored publications will follow.