The Integrated Program in Cellular, Molecular and Biomedical Studies (CMBS) is an umbrella program that presents students with a unique opportunity to obtain individualized training in all aspects of biomedical sciences, including basic cell and molecular biology, microbiology, structural biology, biophysics, genetics, immunology, neurobiology, systems and computational biology, as well as translational biomedical disease-related research. The CMBS program is an accredited degree-granting program that was first established in 1986 to provide interdisciplinary coursework and bridge the basic sciences at Columbia University Medical Center (CUMC). The underlying rationale for this program was to provide graduate students with a thorough grounding in the basics of biochemistry, genetics, cell and molecular biology through a series of 'core courses.'

Participating Faculty:
The CMBS program offers trainees the opportunity to rotate in and carry out thesis research in all areas of basic and translational research at CUMC. The majority of our trainees enter the program as "undifferentiated" individuals who applied to and joined the CMBS program because we offer research opportunities in world-class laboratories from diverse areas of interest. Consistent with this diversity, rotation choices of CMBS trainees are broad. This wide variety of choices of faculty studying such diverse areas is simply not available to students in any other program in the University. The participating faculty are drawn from all the basic science departments at CUMC, including the new Systems Biology Department (see Faculty list.)

Training Program:
The mission of the CMBS program is to provide rigorous training in critical thinking, while giving students a broad base of possible research areas. Our hope is not only to train the next leaders in the field of biomedical research, but also to provide training for future leaders in other areas where a biomedical research background will be of great benefit. Students in the CMBS program have a wide variety of choices of research areas and possibilities. The program in unique in the breadth of the topics from which a student can choose and the tailor-made curriculum that a student can design. The faculty trainers derive from all the basic science graduate programs at CUMC. Many of the faculty trainers are affiliated with both basic science and clinical departments, and are therefore engaged in multiple disciplines. As a result there can be many collaborative and interdisciplinary interactions in the program.

The Program Directors are responsible for most of the direct advising of the students, especially during the first year regarding coursework, rotations and any other issues that arise. They meet with the first year students for formal meetings three times a year, once at the beginning of the year and then at the end of each semester. The students take their qualifying examinations during the first semester of their second year and formal advising is then taken over by the student's thesis committee.

First year students:
The CMBS program and the Office of Graduate Affairs interact with trainees in the summer prior to matriculation to facilitate acquisition of Columbia sponsored housing. Nearly all the incoming students are able to get on-campus housing, although some students prefer to live off campus. Off campus housing is available and facilitated by realtors who have long-standing working relations with Columbia housing administration. Upon arrival at Columbia, the Office of Graduate Affairs (OGA) holds a series of orientation events to acclimatize the students to the campus and the city, including an overnight camping and hiking trip, which gives the incoming students a bonding experience across all the biomedical Ph.D. programs. The CMBS program also sponsors an orientation lunch with the Program Directors. During this orientation meeting, we discuss what their time in the graduate program will be like, including course requirements, laboratory rotations, qualifying examinations, student seminars and any other requirements that they might have during their tenure as graduate students. The Program Directors subsequently meet individually with each student to discuss their own particular training program, as well as their rotation choices.

Rotations:
The most important information that the students must have for rotation selection is the faculty research interests. Many departments offer a Faculty Research Seminar for first year students in the fall, in which faculty present 15-20 minute talks on their research and CMBS students are invited to attend. The students in the CMBS program are also given the opportunity to attend one of the departmental retreats that are held in the beginning of the year. We also invite incoming students to the CMBS Program Retreat the summer before they start. However, given the large number of faculty and areas of research that the students can choose from, the individual orientation interviews with the Program Directors are very important to help guide the students to appropriate laboratories. Students are required to do at least two rotations, but generally do three rotations during their first year. The first rotation goes until winter break (third week in December), the second rotation goes from January-March and the third rotation from April-June. Occasionally it is necessary for a student to do a fourth rotation, although we do not encourage this possibility.

The Program Directors provide extensive input on rotation selection. They also obtain written rotation evaluations from faculty mentors as soon as rotations are complete. Here too, our trainees have generally not encountered any difficulties. However, in the event that trainees encounter complications with rotations, the Program Directors will meet with trainees and rotation mentors independently to discuss problems that arose and how they can be addressed.

Orientation:
During orientation, the Office of Graduate Affairs holds a number of important events. We start with a mini-course that explains how to establish the framework for an experimental project, how to set up a system, design experiments within that system, and how to determine and use the correct set of controls. This course also covers an introduction to rigor and reproducibility in experimentation that is necessary for all the students. Students also get mandatory training in Laboratory Safety, an orientation on sexual violence and response, as well as discrimination, harassment and gender-based misconduct policy. Finally, as part of their orientation session, the students will be given a lecture by the CMBS Program Co-Director on Responsible Conduct of Research (RCR), where they will also receive the publication "On Being a Scientist," as well as Columbia University's institutional RCR policy.

Coursework:
During the first year, students have the following basic curriculum:

fall semester spring semester
Biochemistry, Cell and Molecular Biology I Biochemistry, Cell and Molecular Biology II
Molecular Genetics Statistics for Basic Scientists
CMBS Seminar Elective 1
  CMBS Seminar

 
As an introduction to the Biochemistry, Cell and Molecular Biology course, a boot camp is held, where students review basic principles of Biochemistry. The reasoning behind this boot camp is that incoming students have a variety of educational and experimental backgrounds, so we begin with a brief immersion course on the basics of molecular biology, biochemistry and structural biology.

Second Year Students:
In the second year, students have to take their qualifying examination as well as elective courses. In addition, they take the Responsible Conduct of Research course which includes both lecture and small group sessions. The schedule for year 02 is as follows:

fall semester spring semester
Elective 2 Responsible Conduct of Research (lecture and small group sessions)
Qualifying Examination Student Seminar
Student Seminar  

 
Electives are chosen depending on the student's research area and/or general interest. Students must receive permission from their Program Directors for their choice of electives. Since Columbia also offers many non-science courses to all the students, any student wishing to take such a course must receive permission from their mentor as well as the Program Directors. These courses do not count toward their electives. In years 03-05, CMBS students take the Student Seminar but are not required to take any additional courses.

Qualifying Examination:
During the first semester of their second year, students prepare for their qualifying examination. This examination is used as a formal evaluation of the student's potential as a candidate for the Ph.D. degree. It is designed to assess the student's ability to develop a sophisticated, in-depth understanding of their thesis project and it also serves as a tool for identifying deficiencies in the students' background that could be remedied by further coursework or additional reading.

Students present a written research proposal on their thesis topic. The proposal is written in the format of an NIH fellowship and consists of a description of the background and significance of the topic, specific aims and research approaches to address the aims. Preliminary data, if available, can also be presented but given that the examination is given shortly after the trainee started their project, this is not necessary. The student along with their thesis advisor proposes three possible committee members who will serve as examiners. The Program Directors review the proposed committee members and if they approve, will select one of them as Chair. After the student submits their proposal, an oral examination is scheduled. At this oral examination, the student presents a 'chalk talk' of their proposal and are examined on the proposal, as well as on any other topics that the student should have learned in their coursework.

Other Courses:
During the spring semester of the second year, students take a lecture course in the Responsible Conduct of Research (RCR) and participate in a small group discussion. Students in the Structural Biology / Molecular Biophysics specialization must take two Molecular Biophysics and Structural Biology courses: Molecular Biophysics, Biophysical Chemistry (one taught in conjunction with the Chemistry department), NMR Spectroscopy of Macromolecules and Diffraction Analysis of Macromolecules. Students in the Stem Cell specialization must take the Stem Cell course. Two elective courses are required; among the possible electives are Biochemistry of Nucleic Acids and Protein Synthesis, Chromosome Dynamics & Genome Stability, Cancer Biology, Introduction to Immunology, Membrane Receptors and Transport Proteins, Mechanisms of Human Disease (either of two semesters), Genetic Approaches to Biological Problems, Principles of Developmental Biology, Neural Development, Advanced Topics in Microbiology and Immunology and Advanced Eukaryotic Molecular Genetics. Students in the CMBS Program must take two electives and must maintain a B average.

In addition to course work, all students take part in the CMBS Program Seminar. Other journal and data clubs are topic-related and available to the CMBS Program students.

Thesis Committees:
Either in the summer of the second year or the fall of the third year, the students have their first meeting with their Thesis Committee. The Thesis Committee is typically the same as the qualifying examination committee, although occasionally one of the members might be replaced, especially if the student's research is going in a different direction. This Committee provides scientific expertise related to the student's projects and monitors thesis research. For the first Committee meeting which is held either in the spring or summer of the second year, the student presents a short written report that contains the Specific Aims of their proposal and any progress they have made since the qualifying examination. The Committee discusses with the student the progress to date and the priorities for the order in which the work will proceed, as well as the chosen design of experiments. It is possible that the Committee may recommend changes to the experimental design or priorities. The Committee also decides when to have the next meeting, which can be either in 3, 6 or 9 months, but no longer than one year. For these subsequent meetings, the student prepares a 1-2 page report outlining their progress on the previous aims and presents their timetable for finishing their thesis work. The Committee can and should recommend improvements to experimental strategies and fallback plans for difficult or risky experiments.

Dissertation and Thesis Defense:
After the thesis committee gives its approval for the student to finish writing the thesis, the defense is scheduled. The final thesis committee consists of the mentor, three existing thesis committee members and one additional examiner. If the additional examiner is outside the University, they hav eto be approved by the Program and the Dissertation Office as a competent examiner. The thesis should be submitted to the committee two weeks before the scheduled defense. A public presentation is given immediately before the closed defense. At the time of the closed defense, the student may be asked to make additional revisions that will then need to be approved ny the mentor and one other member of the committee (assigned at the time of the defense.) On rare occasions, the student may be required to do additional experimental work, extensive thesis revisions or a second dissertation defense. Students are required to submit a first author paper before their defense.

Other Specializations within the CMBS Program:

i. Systems and Computational Biology
Over the past decade bioinformatics and computational biology has emerged as a distinct sub-discipline of the life sciences characterized by its uses of computational methods to analyze and predict the results of experiments. Students specializing in computational biology need to learn not only the application of pre-existing computational methods to biology but get in-depth exposure to quantitative disciplines such as computer science, statistics and physics. To satisfy this need, we have established a Systems and Computational Biology specialization in the CMBS Program under the auspices of the Department of Systems Biology. As described in the website, the CMBS Program has modified its requirements for students who participate in the systems/computational biology specialization and we believe that we have developed an extremely strong and cohesive program in Systems and Computational Biology.

ii. Structural Biology and Molecular Biophysics
We have recently added a Structural Biology/Molecular Biophysics specialization to the CMBS program. Students who are interested in structural biology and biophysics therefore have a clear idea where they should apply and also a home program. The students in this specialization take the same core courses as the other CMBS students, except that they also take two courses in Molecular Biophysics and Structural Biology as described earlier. These courses count as the electives for students in this specialization. All other aspects of the program are the same.

iii. Stem Cell Biology and Cell Biology
a. Stem cell biology is a burgeoning area and there are quite a number of students interested in research in this field. We have therefore also added a stem cell biology specialization. Students who choose this specialization will have to take a stem cell course that is taught yearly. There is also a Stem Cell Initiative at CUMC, with a special seminar program, as well as a Stem Cell Day that the students will be requested to attend.

b. Students interested in cell biology can select the Cell Biology specialization in the on-line application. Students interested in cell biology will attend the Cell Biology Research Group seminar that meets biweekly and also attend Cell Biology seminars that are part of the Pathology & Cell Biology seminar program.

iv. The Med into Grad Program
Students in the CMBS program are eligible to apply for our Med into Grad program, which is designed for students to gain familiarity with clinical problems. In addition to taking one semester of the "Mechanisms of Human Disease" course, the students selected for the program are assigned to a clinical mentor in an area related to their research. They generally go to clinic once or twice a month for a half day to see patients. The students meet with the Directors of the program twice a month and present cases that they have observed. This program therefore incorporates an understanding of te principles of medicine and disease into the education of Ph.D. researchers.

Special Features of the CMBS Program:

i. CMBS Student Seminar
In addition to coursework and research, there are several special features of the CMBS Program. The CMBS Program students participate in the CMBS Program student research seminar series. In this series, which is held every other Thursday evening, all third, fourth and fifth year students present their own research to the other students in the program. Attendance for the CMBS Program students is mandatory and monitored by the presenting student. Two students present every other week and the presenting student’s mentor and/or thesis committee member are asked to attend. The student seminar gives the students in the program an idea about the projects that their fellow students are working on and it also gives the students an opportunity to practice a talk on their work before a critical, but friendly audience of their peers, before they have to give this talk either for their thesis defense or when they apply for a post-doctoral position.

ii. CMBS Program Retreat
The second important special feature of the CMBS Program is the biennial program retreat. The most recent retreat was held July 2016 and was organized almost exclusively by CMBS trainees under the supervision of two junior faculty members. The retreat includes talks by students and a few junior faculty as well as research poster presentations. All students after their first year are expected to give a talk or present a poster. A Keynote speaker is also chosen by the student and faculty organizers. Thus both the seminar series and the retreat give our students an excellent chance to present their work in front of a friendly, but diverse audience.

iii. Expanded Career Options Seminar
A new seminar for the CMBS students that we will be starting in the fall is a seminar that will discuss expanded career options. In addition to Individual Development Plans and lecture series associated with them, we think that a smaller group seminar with a discussion session will be even more beneficial to our students. We are therefore preparing a new seminar program aimed at fourth year students and above. The seminar schedule will build upon the successes of prior CUMC trainees and the rich resources within Columbia University. We will invite mid-career professionals who graduated from our program to meet our students and discuss the route from their Ph.D. to their professional careers. Specifically the course is designed to:

• Help students understand the challenge and satisfactions in each selected career pathway
• Identify the strengths and characteristics that are valued in each selected career pathway
• Demonstrate how Ph.D. training in biomedical science would advance their career in the various pathways

Taken together, this information will be helpful for the students to make informative decisions about their own career paths and launch a successful career after graduation.

Admissions:

i. Applications
Students apply directly to the CMBS Program and their applications are evaluated by the Admissions sub-committee. Applicants are expected to have a B.S. or B.A. degree in Chemistry, Biology or a related field and to have completed courses in Biochemistry and Organic Chemistry. All students who are being considered must have pursued undergraduate research or have subsequently had a research position. In addition to the grades and scores, the recommendation letters are important for assessing the motivation and abilities of the applicants that are not reflected in the numerical scores. GRE scores are also required.

Those applicants, who pass through the initial screening by the Admissions committee are invited for a personal interview. The personal interview is particularly important in helping us judge an applicants, especially their scientific sophistication and motivation. Usually about half of the students who are interviewed are accepted. Following the interview, the CMBS Program admission subcommittee ranks the applicants to be accepted. Applicants are admitted to the program on a rolling basis, since acceptance rates vary from year to year. The Associate Dean of Graduate Affairs reads and approves each of the applications that are submitted by the program for admission.

ii. Interview weekends
We invite our top candidates within the U.S. and Canada to visit Columbia for an expense-paid interview before they are accepted. In conjunction with the Office of Graduate Affairs, we have set up a rather elaborate interview and recruitment weekend to help us to evaluate and recruit the prospective students. Prospective students spend the first day of their visit learning about the program, attending a lecture from a member of the training faculty, lunch with current trainees, housing tours and most importantly interviews with 4 faculty trainers. Interviewers are selected for each prospective trainee based on trainee requests and field(s) of interest. At the end of the day, the interviewees go to dinner with a selection of our current students, as well as faculty members. The program directors, coordinator and the Associate Dean make it a priority to attend these dinners as well to get to know the applicants in a more informal setting, as well as answer any questions. On the second day of their visit, applicants participate in social activities sponsored by Office of Graduate Affairs and hosted by the Graduate Student Organization. CMBS trainees and trainees from other programs serve as hosts for activities that include brunch; visits to museums, tourist sights and/or sports clubs, and late night merriment that begins with dinner and ends at jazz or comedy clubs. We believe that these events allow the applicants to get a complete impression about both the exciting scientific atmosphere at Columbia and the cultural advantages of living in New York City.

Students, who are accepted in the CMBS program are notified by e-mail and official letters from the program and the Graduate School. On average, we have 10-15 students entering the program. We accept both US and international students.

Resources and Environment at Columbia:
Columbia University College of Physicians and Surgeons provides an outstanding intellectual and physical environment for biomedical research. Clearly, the greatest strength of the program is the outstanding faculty at Columbia that includes the leaders in almost all the areas of cellular, molecular and biophysical studies. Each department at Columbia has an outstanding seminar series. Furthermore, a number of special distinguished lectures and symposia occur each year. An additional resource of the CMBS Program students is the more than 200 post-doctoral and 200 pre-doctoral students in the various laboratories of the training faculty. Furthermore, the fact that Columbia is part of a premier hospital system with many outstanding clinical departments means that there are a lot of lecture series with a more clinical orientation, including departmental grand rounds that will allow the students in the program to place their research in an important medical context. Clinical fellows and residents also regularly spend part of their training periods in the laboratories of the basic science departments.

In addition to the outstanding intellectual environment, there is a vast array of outstanding core facilities available to the CMBS Program students. One advantage of core facilities at the University is that all shared facilities are available to the entire CUMC research community—even if maintained by individual departments or centers. The breadth of the shared resources available means that any technique, reagent, service, or sample required is likely available through a core facility—and that core is likely in the building next door or across the street, given the proximity of all of the buildings on campus. For in-depth molecular analysis, The Columbia Genome center offers all of the cutting edge next generation sequencing platforms for whole genome and whole exome sequencing, whole transcriptome profiling by RNAseq which includes low input RNAseq and analysis of coding and non-coding RNA, and bioinformatics support to analyze the large datasets obtains. Single cell RNAseq and other approaches are also being optimized by faculty in Systems Biology and new platforms are available. The genome center also offers high throughput screening platforms for small molecule libraries using shRNA, siRNA, cDNA and chemical probes, and different plate-based and bead-based assay platforms, as well as informatics support for these assays. High throughput sequencing, genotyping and bioinformatics support is also available from the Institute for genomic medicine, directed by Dr. David Goldstein a faculty trainer for the CMBS program. The Herbert Irving Comprehensive Cancer Center (HICCC) also offers numerous core facilities and shared resources for use by all investigators at CUMC, including biostatistics support, bioinformatics, confocal microscopy, flow cytometry, genome sequencing, epigenetics analysis and high throughput targeted methylation analysis, molecular structure modeling and crystallography, a molecular pathology core, proteomics, small animal imaging and image-guided irradiators for small animal models. There is also a transgenic and knockout mouse facility for mouse model generation. Other core facilities are available through individual departments and are also open to all CUMC researchers including flow cytometry and confocal microscopy from the Department of Microbiology and Immunology, Flow cytometry (analytical and sorting) and two-photon microscopy offered by the Center for Translational Immunology. There are several Biobank repositories on campus for translational studies maintained by the Institute of Genomic Medicine, the Cancer Center, the CCTI, and the Brain Bank in the Department of Pathology. The Columbia stem cell core facility offers a number of services for human iPSC production, gene editing by CRISPR-Cas9, electrophysiology and stem cell culturing. There are also core facilities for more specialized research funded by NIH, such as the Skin Disease Research center which provides services for dermatopathology, skin cell culturing and analysis, and the Diabetes Research Center (Funded by NIDDK) which provides specialized hormone and metabolite screening, histopathology and mouse phenotyping services. Given that a specific research project requires the use of many different types of technologies, including the acquisition of big datasets and high throughout analyses, these core facilities are invaluable and essential to the students in the CMBS Program.

For data analysis and preparing manuscripts and proposal writing, there is also ample support provided to the students. As indicated above, all of the core facilities providing high throughput sequencing and screening also provide bioinformatics support. Also readily available is biostatistical support through the HICCC in which students can meet individually with statisticians for help with data analysis and/or experimental design and power analysis. For background research and literature review, nearly all the scientific journals are now free on-line through the Columbia University library collection and cost-free literature searches are of course available for all students. There are informationists available to meet with to design and refine database searches. There are courses offered for grant and proposal writing and are available to the graduate students, and a dissertation office provides help and guidance to students preparing their dissertation. Thus, there are ample core facilities and resources for all scientific and academic aspects of graduate training.