Biotechnology Core

The following is a brief highlight of selected case studies showcasing our teams project management expertise and experience.

Background:

The project focused on a structural biology research lab employing x-ray crystallography. The lab’s scientific emphasis focuses on experimental structure determination of high-profile anti-microbial drug targets.

Problem:

The lab had collected a single set of x-ray diffraction data for a protein whose crystal was extremely difficult to grow and for which no additional crystals existed. The lab wanted to reduce development time and cost by using their existing dataset. Unfortunately, the protein structure was not solvable (i.e., the diffraction could not be phased) using state-of-the-art computational methods.

Project Framework:

The complex crystal structure (i.e., the regular yet specific arrangement of each individual protein molecule) caused traditional phasing methods (via the method of molecular replacement) to fail. However, it was known that the protein had arranged itself in the crystal according to a special type of symmetry called non-crystallographic symmetry. We were faced with developing a new computational method to use domain-specific knowledge in conjunction with the existing diffraction data to solve the protein structure.

Outcome:

We developed an efficient computational algorithm to identify molecular poses consistent with the non-crystallographic symmetry present in the underlying crystal. These molecular poses enabled the solution of the protein structure without additional wet lab experimental work. The developed algorithm is general purpose and can be used to exploit non-crystallographic symmetry in a range of structure determination efforts. We worked closely with the client’s lab through all stages of the project, eventually handing the deliverable back to the client when it was clear they could see the project to completion.  The protein structure was successfully solved.  The structure is currently part of a structure-based drug discovery effort to develop novel anti-parasitic pharmacologic compounds.

Background:

Nano-biotechnology company XYZ has two branches, a research branch that focuses on the innovation and development of high-potential technologies at the interface of nano, materials and life-science, as well as a product branch that focuses on transitioning those technologies into products that cater to under-served communities with unmet medical needs. It is now very interested in entering the high-growth molecular analysis and diagnostics market.

Problem:

Nano-biotechnology company wants to know its advantages and limitations in tackling this market. It wants to understand the market both from a technology as well as applications points of view and determines whether it will develop its own tools or hand-shake with the existing companies.

Project Approach:

First, a thorough technology landscape assessment is performed to understand who are the key players in this market, their competitive differentiations defined by the unique aspects of their technologies. This will allow us to determine a. the degree of maturity of the technologies and whether there are alternative technical solutions b. whether there are ways to better existing technologies by enhancing certain components (such as a better engineering approach enabling higher throughput, or a better enzymatic property enabling higher accuracy).

Secondly, these companies are reviewed for their strategic moves to enter the market. Are they leveraging cost advantages or enabling a new application? Do they spend more technical resources to pursue medically relevant discoveries, establish R&D alliances with research institutes and the pharma industry, or licensing new IPs?

Also, what are they doing internationally, especially in developing countries that would allow them to enter these massive markets? Thirdly, we discuss the opportunities that are most appropriate given the company's resource and strength and come forward with a consensus solution.

Most of the information and insights gathered are based on corporate documents, research literature, company interviews as well as conversations with academic opinion leaders. The materials deliverables are in the formats of both written as well as ppt presentations, followed by brain-storming and concluding remarks.

Outcome:

The company is able to achieve the following understanding:

The technology landscape is highly competitive, because of the capital intensive nature as well as the momentum gained by some early entrants, who occupied as much as 60% of the emerging market. To directly compete with these technologies would require long term commitment in capital and expansion of a team highly specialized in supporting basic science research. Therefore, there are two ways to differentiate.

Given the company's technical expertise in nano-science and high-sensitivity biochemical screening, it can form partnerships with existing players by providing modular components and to co-develop next generation technologies. They can create values by providing an end-product in surface materials, molecular screening assays or development methods of them. Another way to differentiate is by focusing on affordability & convenience.

Most current technologies are very expensive and largely immobile, so a large market niche is underserved that requires cheap, portable and useful devices based on medically relevant molecular targets for diagnostics.

Background:

Our challenge consisted of designing a series of experiments to demonstrate that certain proteins do not require a folded structure for their activity.

Problem:

As part of my post-doctoral work I studied the human translation inhibitors, 4E Binding Protein 1 and 2, expecting to determine the 3D structure of these proteins. However, NMR showed that these proteins were not folded, even under a variety of different conditions, and we began to suspect that folding was not necessary for their activity, although at the time this was considered extremely unusual and highly unlikely.

Project Framework:

The challenge was to come up with a series of experiments to show that this was true, which I achieved in the following way. (1) I demonstrated using NMR that the 4E-BPs could bind to their target, a translation factor, starting from the unfolded state and remaining mostly unfolded when bound. (2) I showed that a short peptide corresponding to the binding region of the 4E-BPs could bind to the target and did so in a similar way to the full length proteins. (3) I showed that the same peptide inhibited translation in our assays, like the full length proteins.

Outcome:

This work was published in the journal Biochemistry. We now know that many proteins, perhaps as many as 30% in humans, do not require folded structure for their activity.

Background:

Globalization has become an essential component of business growth strategies for many companies across many industries.

The drivers for globalization are multifaceted and complex.  Three key reasons for globalization are to open new markets, allow organizations to take advantage of huge talent pools, and diversify geographical risk.

For organizations making the transition to a global mind-set it is a major challenge to maintain their own growth trajectory and at the same time develop globalization skills through off shoring and/or developing partnerships.

Problem: 

Despite my organization’s lack of global, our task was to engineer a complex platform product with multiple electrical and subsystem components.

We were required to maintain quality, reduce cost, maintain schedule and meet all worldwide agency approval expected for enterprise class products.

Project Framework:

Our organization’s globalization strategy included establishing an offshore facility. It also meant developing third party engineering and manufacturing partners around the world.

Given that our organization was not experienced in these types of engagements; we needed changes in culture, communication, attitude, and processes.

As manager of this development effort, I sought and received buy-in to a new program plan required to support this global initiative.

We received buy-in from management, key functional groups, and global development partners.  We also worked closely with internal and external cross functional teams to identify and resolve issues quickly.

We engaged and involved our external partners at key decision points and involved them with planning and logistics when possible.

Outcome:

At the completion of the project, a completed platform product was delivered to the company.

Our organization had completed its first globally engineered program, the offshore team had established themselves and our design partner was able to boast of a completing a difficult program working for a demanding customer.

Further, the platform’s quality, reliability and cost had met or exceeded customer expectations.